In recent years, phototherapies, including photodynamic therapy (PDT) and photothermal therapy (PTT), have emerged as novel clinical techniques and gained prominence due to their low toxic side effects, lack of drug resistance, and strong immune activation effects [
[1],
[2],
[3],
[4],
[5]]. PDT is based on the electron or energy transfer between photosensitizers (PSs) and surrounding O
2 to generate reactive oxygen species (ROS) [
6]. These include free radicals (
•OH, O
2−•, etc., type I) and singlet oxygen (
1O
2, type II,
Fig. 1c) [
7]. Through a series of photochemical reactions, these ROS can induce cancer cell apoptosis [
8,
9]. When tumor tissues in the targeted regions are illuminated under light irradiation at a specific wavelength, the growth of tumors can be inhibited by ROS. Unlike PDT, PTT does not require the presence of tissue O
2, thus it can be executed in hypoxic conditions [
[10],
[11],
[12]]. PTT approaches capitalize on the sensitivity of tumor cells to heat, which can also trigger apoptosis [
13,
14]. During the process of cancer treatment, the heat generation by PSs through non-radiative relaxation processes from excited states to the ground state (
Fig. 1c), can induce the apoptosis of tumor cells [
15,
16].
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Fig. 1In the application of phototherapies, the performances of PSs play a decisive role. Among them, PSs with planar rigid conjugate structures have been widely used for phototherapy, such as boron dipyrromethenes (BODIPYs) [
[17],
[18],
[19],
[20]], phthalocyanines [
[21],
[22],
[23],
[24],
[25]], cyanines [
[26],
[27],
[28],
[29],
[30]], and perylene bisimides [
[31],
[32],
[33],
[34]]. Different from these several PSs, porphyrins, which were first discovered as the form of hematoporphyrin in human blood in 1841 [
35], and proposed by William Küster in 1912 [
36], are a class of large heterocyclic compounds formed by the
α-carbon atoms of four pyrrole-like subunits interconnected
via methylene bridges with highly conjugated systems (
Fig. 1a) [
37]. Thanks to their strong light absorption in the Soret band (around 400 nm) and Q-band (500–700 nm) (
Fig. 1b) [
37], along with other versatile properties, porphyrins have become common model compounds in biomimetic chemistry and functional molecules for a variety of applications such as catalysis [
38,
39], light-harvesting syetems [
40,
41], chemosensing [
42], and phototherapy [
[43],
[44],
[45]]. Porphyrins and their derivatives widely exist in living organisms in nature and are the core structures of many essential molecules of life, such as heme, chlorophyll, vitamin B12 and cytochrome, etc. Moreover, many porphyrins exist in nature in the form of coordination with metal ions, such as chlorophyll containing a coordination structure of chlorin and magnesium, and heme coordinated with iron. Thus, they exhibit good biocompatibility [
[46],
[47],
[48]]. Moreover, numerous ones among them have been approved for clinically treating lung, skin, and esophageal cancers, etc. (
Table 1) [
49,
50]. For instance, the first-generation of porphyrins represented by hematoporphyrin derivatives, the second-generation of porphyrins represented by mTHPC and Chlorin e6 (Ce6) [
51]. It is worth noting that the clinically approved the first- and second-generation of porphyrin PSs are predominantly utilized in PDT. Currently, the only PS approved for clinical PTT is indocyanine green (ICG) [
52].
Table 1. Several representative porphyrins approved for clinical applications or trials.
| PSs | Generation | Initial approval | Maximum absorption wavelength (nm) | Molar extinction coefficient
(M–1 cm–1) | Yield of 1O2 | Refs. |
|---|
| Photofrin® | First | 1993, Canada | 630 | 3.00 × 103 | 11% | [53] |
| HiPorfin® | First | 2006, China | 630 | 1.26 × 103 | 12% | [54] |
| Verteporfin® | Second | 1999, FDA (US) | 689 | 4.00 × 104 | 78% | [55] |
| mTHPC (Foscan, Temoporfin®) | Second | 2001, EMA (Europe) | 650 | 3.00 × 104 | 30% | [56] |
| Mono-l-asparty Ce6 (Talaporfin®, NPe6) | Second | 2003, Japan | 654 | 4.00 × 104 | 77% | [57] |
| Padeliporfin® | Second | 2017, EMA (Europe) | 755 | 1.09 × 105 | 23% | [58] |
| Pheophorbide a | Second | Clinical trials | 667 | 4.45 × 104 | Not reported | [59] |
Although numerous first- and second-generation of porphyrins have been approved for clinical applications or trials, they still have significant shortcomings when applied to phototherapy. For example, the first-generation of porphyrins face substantial challenges, including weak absorption in the near-infrared (NIR) region, low
1O
2 production, high skin phototoxicity, and obvious individual differences in clinical treatment effects [
49]. Due to these disadvantages, the first-generation of porphyrins were not widely used in the treatment of solid tumors [
35]. Compared with the first-generation of porphyrins, the second-generation of porphyrins have shown significant improvement with enhanced
1O
2 yields and red-shifted absorption (
Table 1) [
60]. However, these free porphyrin small molecules always exist many disadvantages in terms of phototherapy efficiency and clinical applications. For instance, their hydrophobic planar and rigid structures limit their water solubility and tend to aggregate easily in water, reducing their ROS-generating capabilities. Additionally, their tissue penetration and tumor targeting abilities are still unsatisfactory. These drawbacks seriously affect their applications in organisms for PDT and PTT [
61,
62]. Encouragingly, in recent years, the development of nanotechnology can address various problems existing in the above-mentioned porphyrin phototherapy, and a large number of reports on phototherapy by constructing nanomaterials loaded with porphyrins have emerged [
63]. Porphyrin-based nanomaterials can be regarded as the third-generation of PSs [
49], and they have the following advantages for phototherapy: adjustable shapes and sizes, increased penetration depth into tissues with NIR excitation, improved photostability, and ease of surface functionalization, etc. [
64]. Among them, supramolecular assembly based on non-covalent interactions (hydrogen bonding interactions, van der Waals forces, π–π interactions, dipole-dipole interactions, hydrophobic and hydrophilic interactions, etc.) is an efficient way to construct multifunctional nanostructures for phototherapy [
[65],
[66],
[67]]. In addition to the above merits of nanomaterials, the highly flexible, well-defined, controlled, and ordered architectures assembled through supramolecular interactions have many unique advantages. For example, they can avoid the time-consuming and tedious organic syntheses [
7], possess abundant stimulus responsiveness and targeting ability [
66], and enable dynamic molecular recognition [
68], thereby showing significant potential in drug delivery, disease detection and treatment [
69]. Fortunately, the facilely functionalized structures of porphyrins are suitable for utilization as versatile building blocks for supramolecular assembly [
39,
47]. Thus, through reasonable design and functionalization, porphyrins can be assembled into supramolecular nano-structures, providing novel strategies to optimize the performance of porphyrins and overcome their limitations in phototherapy [
70]. The porphyrins in these nano-assemblies show a red-shifted absorption wavelength to NIR (Suitable for deep-tissue penetration), enhanced water solubility, more efficient tumor accumulation
via the enhanced permeability and retention (EPR) effect, and the ability to produce ROS or heat [
40,
71,
72]. Therefore, supramolecular assembly strategies for constructing nanomaterials have great application prospects in the fields of PDT and PTT [
61,
62].
However, the previously reported reviews on porphyrin phototherapy have not comprehensively and systematically introduced the utilization of supramolecular assembly strategies to improve their PDT and PTT performances [
72]. Most of these reviews mainly focus on constructing porphyrin-based various nanomaterials, including inorganic nanomaterials [
47,
63]. Some reviews summarize many other aspects of the applications of porphyrin-based self-assembled nanomaterials, such as energy conversion, storage, biomedicine, and environmental protection [
39,
46]. They do not specifically focus on porphyrin phototherapy. Additionally, many supramolecular assembly strategies for constructing porphyrin nanostructures, like porphyrin-based macrocycles or host–guest complexes, were not introduced. There are also some relatively early-reported reviews that lack the latest progress in recent few years on the phototherapy applications of porphyrins [
37,
51]. Moreover, they only focus on the PDT applications of porphyrins and lack coverage of PTT. To the best of our knowledge, at present, only a very few of supramolecular porphyrin PSs have been approved for clinical application, and they are limited to PDT, such as liposomal formulation of verteporfin [
73,
74]. Most researches on the third-generation of porphyrins are still in the basic research stage. That is, it is still in the stage of animal experiments and there is a long way to go before the clinical application. In view of the above research background, herein, we comprehensively summarize the supramolecular assembling strategies for porphyrin-based phototherapy and the existing challenges in designing and constructing various porphyrin-based nano-assemblies. In each section, the supramolecular assembling strategies for porphyrin phototherapy are discussed in detail (See
Table 2,
Table 3,
Table 4,
Table 5,
Table 6,
Table 7,
Table 8,
Table 9). For example, there is the self-assembly of porphyrin-based small molecular amphiphiles and co-assembly of porphyrins with the other small molecules, the self-assembly of various macrocycles constructed by porphyrins, the self-assembly of polymeric porphyrin-based amphiphiles and porphyrin-encapsulated polymers, and the self-assembly of porphyrin-involved host–guest complexes. Moreover, some treatment effects of porphyrin-based assemblies used
in vitro or
in vivo experiments are also presented in the form of Figures, followed by an introduction of the problems and challenges existing in each supramolecular assembly strategy [
75]. We hope to offer a valuable and insightful resource for researchers interested in porphyrin-based supramolecular phototherapies and encourage them to develop more excellent porphyrin-based supramolecular functional materials for the future clinical applications.
Table 2. Summary of the self-assembled porphyrin-based small molecular amphiphiles for phototherapy.
| Type of amphiphiles | Morphology | Supramolecular interactions | Content of porphyrin | Size and stability | Yield of ROS | PCE | Applications | Figs | Refs. |
|---|
| Porphyrin-based lipids | NVs | Hydrophilic-hydrophobic interaction | Not reported | ∼100 nm, enzymatic degradation | None | Not reported | PAI and PTT | None | [77] |
| NPs | Hydrophilic-hydrophobic interaction | 49.8% | ∼60 nm | Not reported | None | MRI-guided PDT | None | [79] |
| NVs | Hydrophilic-hydrophobic interaction | Not reported | ∼90 nm, GSH induced degradation | >100-fold increased | Not reported | Synergistic photoimmunotherapy | None | [82] |
| NPs | Hydrophilic-hydrophobic interaction | 38.5% | ∼33 nm, stable | Not reported | None | Tumor hypoxia relief to enhance PDT | None | [83] |
| NPs | Hydrophilic-hydrophobic interaction | 50% in molar ratio | ∼10 nm, stable | 34% | None | Complementing cancer PDT | None | [84] |
| NVs | Hydrophilic-hydrophobic interaction | 2% and 65% | 2% Pp18-lipos: 96nm; 65% Pp18-lipos: 129 nm, stable | Not reported | Not reported | PDT/PTT triggering immune activation | Fig. 2 | [85] |
| NPs | Hydrophilic-hydrophobic interaction | 90%, 67%, and 52% | 75–95 nm, good serum stability | Not reported | None | Intracellular uptake of NPs for PDT | Fig. 3 | [86] |
|
| Type of amphiphiles | Morphology | Supramolecular interactions | Content of porphyrin | Size and stability | Yield of ROS | PCE | Applications | Figs | Refs. |
|---|
| OEG-modified porphyrins | NPs | Hydrophilic-hydrophobic interaction | 12.4% | ∼82 nm, stable | Not reported | Not reported | Multimodal imaging guided PDT/PTT | None | [87] |
| NPs | π−π stacking | Not reported | ∼120 nm, good stability | None | 62.5% | PAI-guided PTT | None | [91] |
| Not reported | Hydrophilic-hydrophobic interaction | Not reported | Not reported | 50–60% | None | Two-photon PDT | None | [93] |
| NPs | Hydrations and π−π interactions | Not reported | 60–80 nm, good photostability | 87% | None | Enhanced NIR absorbance and PDT | None | [95] |
| Fusiform-like NPs | Hydrophilic-hydrophobic interaction | Not reported | 190 nm × 100 nm, controlled release | Not reported | None | Chemotherapy/ferroptosis/immunomodulation | None | [94] |
| NPs | π−π stacking and hydrophilic interactions | Not reported | 50–100 nm, high colloid- and
photo-stability | None | 70% | NIR-II imaging guided PTT-immunotherapy | Fig. 4a | [97] |
| NPs | π−π stacking and hydrophilic interactions | Not reported | 150–200 nm, high stability | Not reported | 52.7 % and 64.3 % | PDT and PTT | Fig. 4b | [98] |
| NPs | π−π stacking, hydrogen bonding, hydrophilic and hydrophobic forces | Not reported | 99.8 nm, simulated drug release | 24.3% | None | Synergistic PDT and chemotherapy | Fig. 4d | [99] |
|
| Type of amphiphiles | Morphology | Supramolecular interactions | Content of porphyrin | Size and stability | Yield of ROS | PCE | Applications | Figs | Refs. |
|---|
| Porphyrin-based peptides | Nanodots | π−π stacking and hydrophilic interactions | Not reported | ∼25 nm, long-term colloidal stability | None | 54.2% | PTT | None | [101] |
| NFs | π−π stacking and hydrophilic interactions | Not reported | 30 ± 5 nm, stable | None | Not reported | PAI and PTT | None | [103] |
| Not reported | π−π stacking and hydrophilic interactions | Not reported | Not reported | 31% | None | Epstein-Barr virus-targeting PDT | None | [104] |
| NPs | Hydrophilic-hydrophobic interaction | Not reported | 150.6 ± 15.6 nm, stable | Not reported | None | Acidity-responsive tumor-targeted PDT | None | [106] |
| NPs | π−π stacking and hydrophilic-hydrophobic interaction | 25.1% | 54.9 ± 3.7 nm, relative stable | Not reported | None | Cell membrane-targeting PDT | None | [107] |
| NPs to cylinder | Hydrophilic-hydrophobic interaction | Not reported | ∼220 nm, stable | Not reported | None | Tumor-acidity-responsive PDT | None | [108] |
| Not reported | Hydrophilic-hydrophobic interaction | Not reported | Not reported | Not reported | None | Cell penetrating peptide targeting PDT | None | [109] |
| NPs | π−π stacking and hydrophilic interactions | 2–6% | ∼146 nm, relatively stable | Not reported | None | Cancer stem cells ribosome targeting PDT | None | [110] |
| NPs | Hydrophilic-hydrophobic interaction | 84.8% | ∼118 nm, stable | Not reported | None | PDT for metastatic breast cancer treatment | None | [111] |
|
| Type of amphiphiles | Morphology | Supramolecular interactions | Content of porphyrin | Size and stability | Yield of ROS | PCE | Applications | Figs | Refs. |
|---|
| Porphyrin-based peptides | NPs | Hydrophilic-hydrophobic interaction | Not reported | 128.5 ± 1.2 nm, stable | Not reported | None | PDT enhancing immunotherapy | None | [113] |
| NPs | Hydrophilic-hydrophobic interaction | Not reported | 102.3 ± 0.95 nm, relatively
stable | Not reported | None | PDT amplified immunotherapy | None | [114] |
| NPs | Hydrophilic-hydrophobic interaction | Not reported | 76.7 ± 5.2 nm, shape-transformable | Not reported | None | Chemo-PDT for breast cancer | None | [115] |
| NPs | Hydrophilic-hydrophobic interaction | Not reported | 55.99 ± 5.72 nm, stable | Not reported | None | PDT | None | [116] |
| NPs to NFs | Hydrophilic-hydrophobic interaction | Not reported | 20−24 nm, stable | Not reported | 51.5% | Synergistic PDT/PTT | Fig. 5 | [100] |
| NPs to NFs | van der Waals, hydrophobic,
electrostatic, π−π stacking and hydrogen-bonding interactions | Not reported | ∼160 nm, shape-transformable | Not reported | None | Acid-activatable nanosystem for PDT | Fig. 6a | [119] |
| NFs | Hydrophilic-hydrophobic interaction | Not reported | 22.1 nm, stable | Enhanced yield | None | PDT of oral tumor | Fig. 6d | [120] |
| NFs | Hydrogen-bonding, van der Waals, π−π stacking and electrostatic interactions | Not reported | 7–15 nm, controlled release drug | Not reported | None | Self-delivery of lonidamine and PDT | None | [112] |
| NPs and NFs | Hydrogen bonding, π−π stacking and hydrophilic-hydrophobic interaction | Not reported | NPs: 70 nm; NFs: 25 nm in diameter, shape-transformable | Up to 49.4% | Up to 48.0% | Amino-acid-encoded PTT | None | [121] |
|
| Type of amphiphiles | Morphology | Supramolecular interactions | Content of porphyrin | Size and stability | Yield of ROS | PCE | Applications | Figs | Refs. |
|---|
| Ionic groups-modified porphyrins | Shell-core structure | π−π stacking and electrostatic interactions | Not reported | ∼100 nm, excellent
colloidal stability | Effective ROS generation | Effective photothermal efficacy | PAI-guided PDT and drugs delivery | None | [127] |
| Not reported | Not reported | Not reported | Not reported | 8-fold enhancement | None | Tooth whitening and biofilm eradication | None | [122] |
| Ultra-small nanoassembly | π−π stacking | Not reported | ∼6 nm, stable | Elevated ROS generation
capability | None | Sonodynamic antibacterial therapy | None | [123] |
| Not reported | Not reported | Not reported | Not reported | Not reported | None | Photoactivated hydride therapy | None | [124] |
| NFs | π−π stacking and electrostatic interactions | Not reported | 14.9 ± 2.5 nm, stable | 110-fold enhancement | None | Mitochondria targeting PDT | Fig. 7a | [125] |
| Not reported | π−π stacking and electrostatic interactions | Not reported | No size reported, high
photostability | Enhanced ROS generation efficacy | None | PDT for hypoxic tumor therapy | Fig. 7b | [126] |
Glycosyl modified
porphyrins | NPs | Hydrogen bonding, π−π stacking and hydrophobic interactions | Not reported | ∼170 nm, Hyal-responsive release | Not reported | None | PDT activatied antibiotic | Fig. 8a | [130] |
| Not reported | Hydrogen bonding, π−π stacking interactions | Not reported | < 30 nm, stable | > 40% | None | Targeted PDT | Fig. 8b | [131] |
Table 3. Summary of co-assembly of porphyrins with other small molecules for phototherapy.
| Co-assembly strategies | Morphology | Supramolecular interactions | Content of porphyrin | Size and stability | Yield of ROS | PCE | Applications | Figs | Refs. |
|---|
| Co-assembly of porphyrins with chemotherapeutic agents | NPs | Hydrogen bonding, π−π stacking, and hydrophobic interactions | 67.3 ± 0.7% | 86.2 ± 0.8 nm, slowly releasing drugs | 6.1-fold enhancement | 61.3% | Chemotherapy, PDT, and PTT | Fig. 9a | [132] |
| NPs | π−π stacking and hydrophilic interactions | Not reported | 141 ± 2.1 nm, releasing drugs at acidic conditions | 26% | None | PDT for breast cancer | None | [133] |
| NPs | Hydrogen bonding and π−π stacking interactions | 37.5% | ∼160 nm, good stability | Not reported | 41.9% | Combined PDT and PTT | Fig. 9b | [134] |
| NPs | π−π stacking, hydrogen bonding and coordinations | Not reported | ∼107 nm, slowly releasing drugs | Not reported | None | Ferroptosis boosted oral cancer PDT | None | [135] |
| Co-assembly of porphyrins with other individual small molecules | NPs | Electrostatic force, π−π stacking,
hydrophobic interactions | 30–80% | 20–200 nm, releasing drugs responsive to environmental alterations | Not reported | None | Anticancer PDT | None | [139] |
| NPs | Electrostatic interaction | 50% in molar ratio | ∼100 nm, stable | Enhanced
production | None | PDT | None | [140] |
| NRs, NSs and NPs | π−π stacking, hydrophilic-hydrophobic interactions | Not reported | 65 nm × 26 nm for NRs, 110 nm for NSs, 40 nm for NPs | Structure-dependent 1O2
evolution rate | None | PDT | Fig. 10a | [141] |
| NPs | Hydrogen bonding, π−π stacking | 50% in molar ratio | ∼46 nm, satisfactory stability | Negligible | 40.8% | PTT-enhanced wound healing | Fig. 10c | [145] |
| NPs | Hydrogen bonding, π−π stacking | 2% | ∼110 nm, stable | Not reported | 32.7% | Highly efficient type I PDT and PTT | Fig. 11 | [146] |
Table 4. Summary of porphyrin-based macrocycles for phototherapy.
| Types of macrocycles | Morphology | Supramolecular interactions | Content of porphyrin | Size and stability | Yield of ROS | PCE | Applications | Figs | Refs. |
|---|
| Metal coordinated porphyrin-involved macrocycles | Spherical morphology | Coordination and hydrophilic-hydrophobic interactions | Not reported | 400 ± 18.8 nm, degraded in a weak acid environment | Not reported | None | Synergetic chemotherapy−PDT | Fig. 12a | [161] |
| Spherical structures | Coordination and hydrophilic-hydrophobic interactions | Not reported | ∼38 nm, no stabilty reported | 4 times as efficient as TPP | None | PDT | Fig. 12b | [162] |
| NPs | Coordination and hydrophilic-hydrophobic interactions | 46.4% | 63.6 nm, high
colloidal stability | 44% | None | Cancer photochemotherapy | None | [163] |
| NPs | Coordination and hydrophilic-hydrophobic interactions | Not reported | 61 nm for O-NPs, 58 nm for C-NPs, good stability | O-NPs
was about 155 times faster than C-NPs | None | Light-controlled PDT | Fig. 13a | [164] |
| NPs | Coordination and hydrophilic-hydrophobic interactions | 65% | 134 ± 13.7 nm, stable | Not reported | None | Tumor hypoxia imaging and chemotherapy | Fig. 13c | [165] |
| Nanocages without metal coordination | Single-molecular NPs | Hydrophilic-hydrophobic interactions | Not reported | 34.6 ± 1.8 nm, high stability
in a physiology environment | Not reported | None | PDT | Fig. 14 | [149] |
| NPs | Dynamic covalent self-assembly, hydrophilic-hydrophobic interactions | Not reported | 182.9 ± 15.6 nm, chemically degradable | Not reported | None | PDT | None | [160] |
Table 5. Summary of polymeric porphyrin-based amphiphiles for phototherapy.
| Polymerizing type | Morphology | Supramolecular interactions | Content of porphyrin | Size and stability | Yield of ROS | PCE | Applications | Figs | Refs. |
|---|
| PEG-functionalized porphyrins | NMs | Hydrophilic-hydrophobic interactions | Not reported | ∼20 nm, pH-sensitive releasing PTX | Not reported | None | Cooperative chemotherapy and PDT | None | [96] |
| NPs | π−π stacking, hydrophilic-hydrophobic interactions | 88.9% | ∼100 nm, drug releasing in acidic organelles | None | Not reported | Synergistic PTT and chemotherapy | None | [181] |
| NMs | Hydrophilic-hydrophobic interactions | 86.8% | 121.2 ± 1.2 nm, ROS-triggered drug releasing | Not reported | None | Light-triggered chemo-PDT | None | [182] |
| pH-sensitive NPs | π−π stacking, hydrophilic-hydrophobic interactions | 18.2% | ∼80 nm, pH-sensitive DOX releasing | None | 28.4% | PAI-guided chemotherapy/PTT | None | [183] |
| NPs | Hydrophilic-hydrophobic interactions | Not reported | ∼171 nm, good kinetic stability | Not reported | None | Inflammation imaging and PDT | Fig. 15a | [185] |
| NMs | π−π stacking, hydrophilic-hydrophobic interactions | 93% | 60.6 nm, pH-sensitive mitoxantrone releasing | Not reported | None | Chemo-PDT combination therapy | Fig. 15b | [186] |
| Tumor-targeting NPs | Electrostatic, π-π stacking and hydrophilic-hydrophobic interactions | Not reported | 77.39 ±5.0 nm, release of MSA-2 at pH 5.0 | Not reported | Not reported | Synergistic photo-/immuno-therapy | None | [187] |
|
| Porphyrin-based alternating copolymers | Vesicles | π-π stacking and hydrophobic interactions | Not reported | ∼161 nm, stable | None | 54.1% | PTT for bacterial ablation and wound disinfection | Fig. 16 | [188] |
| Chitosan nano-assembly | Hydrogen bonding and hydrophobic interactions | 1.2% | 132.9 ± 2.8 nm, good colloidal stability | 80.0% | None | PDT for antibiotic-resistant bacteria | None | [190] |
| NPs | Hydrogen bonding and hydrophobic interactions | Not reported | 174.4 nm, size increasing under light irradiation | Not reported | None | PDT | None | [191] |
| NPs | Hydrophilic-hydrophobic interactions | 50% in molar ratio | 87–186 nm, size increasing with increasing length of the POEGMA block | 55–84% | None | PDT | None | [193] |
| NPs | π-π stacking and hydrophilic-hydrophobic interactions | 50% in molar ratio | ∼133 nm, good stability | None | 66% | PTT | Fig. 17 | [194] |
| NPs | Hydrophilic-hydrophobic interactions | Not reported | ∼100 nm, light triggered
porphyrin release | 75%–91% | None | PDT | Fig. 18a | [195] |
| NPs | Electrostatic effect, hydrogen bonding interactions | 94% | < 200 nm, ROS-
degradable | 65%–87% | None | Synergistic PDT and gene therapy | Fig. 18b | [196] |
|
| Polymerizing type | Morphology | Supramolecular interactions | Content of porphyrin | Size and stability | Yield of ROS | PCE | Applications | Figs | Refs. |
|---|
| Porphyrin-based block copolymers | NPs | Hydrophilic-hydrophobic interactions | 1.3%, 3.8% and 7.5% | ∼20 nm, stable | Up to 35% | None | Polymer-dot-sensitized PDT | None | [176] |
| NPs | Hydrogen bonding and hydrophobic interactions | 58.9% | Up to 1300 nm, temperature, ionic and pH responsive | None | 25.3% | PTT | None | [198] |
| Polymer coatings | Polymer coatings on SiO2 surfaces | Maximum 20 % | Not reported | Not reported | None | Antibacterial PDT | None | [199] |
| NPs | Hydrogen
bonding and hydrophilic-hydrophobic interactions | Not reported | 127.7 nm, temperature-responsive disassembly | Not reported | None | Photothermal-activated PDT | None | [200] |
| Unimolecular NPs | Coordination and hydrophilic-hydrophobic interactions | Not reported | 10–30 nm, with excellent temperature
and pH stability | Not reported | None | Synergistic PDT and radiotherapy | None | [201] |
| NPs | π–π stacking and hydrogen bonding interactions | Not reported | ∼135 nm, temperature-responsive disassembly | Not reported | None | NIR-activated “OFF/ON” PDT | None | [203] |
| NPs | π–π stacking and hydrogen bonding interactions | ∼60% | 147.31 nm and 170.57 nm, 1O2-responsive degradation | Not reported | None | Self-amplified PDT | Fig. 19a | [204] |
| NPs | π–π stacking and hydrogen bonding interactions | Not reported | ∼150 nm, acid-triggered dissociation | Not reported | None | Antibacterial PDT | Fig. 19b | [205] |
Table 6. Summary of porphyrin-encapsulated amphiphilic polymers for phototherapy.
| Morphology | Supramolecular interactions | Content of porphyrin | Size and stability | Yield of ROS | PCE | Applications | Figs | Refs. |
|---|
| NMs | Coordination, π–π stacking and hydrophilic-hydrophobic interactions | 12.4% | ∼80 nm, stable | Not reported | Not reported | Multimodal imaging guided synergistic PDT/PTT | None | [87] |
| NPs | π–π stacking and hydrogen bond interactions | 69.6% | ∼190 nm, enhanced stability | Not reported | None | Controllable photobiomodulation and PDT | None | [206] |
| NPs | π–π stacking and hydrogen bonding interactions | 87.6% | ∼200 nm, enhanced stability | Not reported | None | Photodynamic antimicrobial chemotherapy | None | [207] |
| NPs | Electrostatic adsorption, hydrophilic-hydrophobic interactions | Not reported | ∼100–110 nm, stable | Not reported | None | Chemo-PDT of drug-resistant bacterial infection | None | [208] |
| NPs | Hydrogen bonding and hydrophobic interactions | 3.5% | 194 nm, PDT-driven CO release | Not reported | None | Synergistic PDT and CO gas therapy | None | [209] |
| Spherical morphology | Hydrogen bonding and hydrophobic interactions | 5% | ∼174–193 nm, NO release | Not reported | None | NO/photodynamic synergistic treatment | None | [210] |
| NPs | Hydrogen bonding and hydrophobic interactions | 97% | <200 nm, with long-term stability | 36% | None | Light-assisted anticancer PDT | None | [215] |
| NPs | Hydrogen bonding and hydrophilic-hydrophobic interactions | Not reported | 124 nm ± 1.85 nm, stable | Not reported | None | Antibacterial PDT | None | [211] |
| NPs | Hydrophilic-hydrophobic interactions | Not reported | 74–95 nm, low releasing PSs | 54–89% | 31.2–49.5% | Synergistic PDT and PTT | None | [212] |
|
| Morphology | Supramolecular interactions | Content of porphyrin | Size and stability | Yield of ROS | PCE | Applications | Figs | Refs. |
|---|
| NPs | Electrostatic and π–π stacking interactions | Not reported | Average diameter of 50 ± 10 nm, good stabilty | Not reported | Not reported | Dual-modal PDT/PTT | None | [214] |
| NPs | Hydrogen bonding and hydrophilic-hydrophobic interactions | 16.5% | 20–80 nm, stable | Not reported | None | Catalytic reaction enhancing PDT | None | [213] |
| Nanofibrous mats | Hydrogen bonding and electrostatic interactions | 0.02%–0.5% | 384 nm–442 nm, good thermostability | Not reported | None | PDT for combating wound infection | Fig. 20a | [216] |
| NPs | Hydrogen bonding and hydrophilic-hydrophobic interactions | 32.9% | 43.0 nm, stable | 68.3% | None | Photodynamic ablation of drug-resistant biofilm | Fig. 20c | [217] |
| NPs | Hydrogen bonding and hydrophilic-hydrophobic interactions | 12% | ∼180 nm, H2O2-responsive releasing TAPP | 45% at pH 7.4 and 60% at pH 5.5 | None | pH/H2O2 dual triggered antibacterial PDT | Fig. 21a | [218] |
| NPs | Electrostatic, hydrogen bonding and hydrophilic-hydrophobic interactions | Not reported | ∼150 nm, ROS responsive
drug release | Not reported | None | Chemotherapy, PDT and cancer immunotherapy | Fig. 21d | [219] |
| NPs | π–π stacking and hydrophilic-hydrophobic interactions | Not reported | 32 ± 3 and 215 ± 26 nm, good stability | None | 60% and 69% | PAI and efficient NIR-II PTT | Fig. 22 | [220] |
| NPs | π–π stacking and hydrophilic-hydrophobic interactions | 10.5% | ∼100 nm, GSH-triggered controlled drug release | Not reported | None | Potent cancer radioimmunotherapy | Fig. 23 | [221] |
Table 7. Summary of porphyrins self-assembly via host–guest interactions with CDs for phototherapy.
| Morphology | Supramolecular interactions | Content of porphyrin | Size and stability | Yield of ROS | PCE | Applications | Figs | Refs. |
|---|
| NPs | Hydrogen bonding and hydrophilic-hydrophobic interactions | 0.013% | ∼70 nm, stable | 37% | None | ALP-activated chemiluminescence PDT for liver cancer-specific theranostics | None | [235] |
| NVs | Electrostatic, hydrogen bonding and hydrophilic-hydrophobic interactions | 74% | Not reported | Not reported | None | PDT | None | [236] |
| NPs | Hydrogen bonding and hydrophilic-hydrophobic interactions | Not reported | 106 ± 1.8 nm,disassembly under light irradiation | 52% | None | Chemo-PDT against cisplatin resistant cancer cells | None | [238] |
| NPs | Hydrogen bonding and hydrophilic-hydrophobic interactions | Not reported | ∼150 nm, good photostability | Not reported | None | Linear alternating supramolecular assemblies for enhanced PDT | Fig. 24 | [239] |
| Spherical NPs | Hydrogen bonding and hydrophilic-hydrophobic interactions | Not reported | 74.1 nm, photocontrollable releasing porphyrin | 50% (before disassembled), 46% (after disassembled) | None | Photocontrollable release and enhancement of PDT | None | [151] |
| NPs | Hydrogen bonding and hydrophilic-hydrophobic interactions | 80.4% | ∼164 nm, disassembly
under reductive environment | Not reported | None | Combinational PDT and chemotherapy | None | [240] |
| NPs | Hydrogen bonding and hydrophilic-hydrophobic interactions | Not reported | ∼121 nm, photocleaved disassembly | Increasing by ∼60-fold | None | PDT and self-cleavable drug release | None | [241] |
| NPs | Electrostatic, hydrogen bonding and hydrophilic-hydrophobic interactions | Not reported | ∼90 nm, stable | Not reported | None | Synergistic gene-PDT | None | [242] |
| NPs | Hydrogen bonding and hydrophilic-hydrophobic interactions | 2.0% | 224 nm, stable | Not reported | None | PDT in solid tumor | None | [243] |
| Not reported | Hydrogen bonding and hydrophobic interactions | Not reported | Not reported | Up to 84% | None | Highly membrane-permeable PDT | None | [244] |
|
| Morphology | Supramolecular interactions | Content of porphyrin | Size and stability | Yield of ROS | PCE | Applications | Figs | Refs. |
|---|
| Spherical shape | Hydrogen bonding and hydrophilic-hydrophobic interactions | Not reported | 110 nm, pH-responsive disassembly | Not reported | None | CRET-induced PDT | Fig. 25 | [245] |
| NPs | Hydrogen bonding and hydrophilic-hydrophobic interactions | 7.4 % | ∼200 nm, stable | Not reported | None | PDT of deep-seated tumors | Fig. 26 | [246] |
| NPs | Hydrogen bonding and hydrophilic-hydrophobic interactions | Not reported | ∼100 nm, stable | Not reported | None | Biofilm microenvironment activated PDT of bacterial keratitis | Fig. 27a | [247] |
| NMs | Hydrogen bonding and hydrophilic-hydrophobic interactions | Not reported | ∼150 nm, stable | Not reported | None | PDT against P. aeruginosa | Fig. 27b | [248] |
| Spherical structure | Electrostatic, hydrogen bonding and hydrophilic-hydrophobic interactions | 1.9% | 136.3 ± 2.1 nm, pH- and GSH-sensitive release | Not reported | None | NO synergistic photodynamic eradication of biofilms | None | [250] |
| NPs | Hydrogen bonding and hydrophilic-hydrophobic interactions | Not reported | 86.0 ± 0.9 nm, GSH-sensitive release | Not reported | None | Combinatory photoimmunotherapy of pancreatic cancer | Fig. 28 | [249] |
| NPs | Hydrogen bonding and hydrophilic-hydrophobic interactions | 14.8% | ∼120 nm, stable | Increasing by 13.3-fold | None | Fluorinated CD nanoassembly enabling O2-enriched PDT | None | [251] |
Table 8. Summary of porphyrins self-assembly via host–guest interactions with CBs for phototherapy.
| Morphology | Supramolecular interactions | Content of porphyrin | Size and stability | Yield of ROS | PCE | Applications | Figs | Refs. |
|---|
Micelle-like
structures | Ion-dipole and hydrophobic interactions | Not reported | ∼600 nm, stable | 7.5 times enhancement | None | Antibacterial PDT | None | [61] |
| Not reported | Electrostatic, coordination, ion-dipole and hydrophobic interactions | Not reported | Not reported | Not reported | None | Photoinduced activation of antibacterial PDT | None | [256] |
| Not reported | Hydrogen bonding, ion-dipole and hydrophobic interactions | Not reported | Not reported | ∼80%, | None | “Clicked” porphyrin-CB conjugate for PDT | None | [257] |
| Not reported | Electrostatic, ion-dipole and hydrophobic interactions | Not reported | Not reported | 74% | 59.3% | Adaptable PDT/PTT | None | [258] |
| NCs | Hydrogen bonding, ion-dipole and hydrophobic interactions | 0.6% | 230 ± 50 nm, Ce6 was released | Not reported | None | PDT | None | [259] |
| Not reported | Hydrogen bonding, ion-dipole and hydrophobic interactions | Not reported | Not reported | Not reported | None | Photodynamic antimicrobial and cancer therapy | None | [260] |
| NPs | Hydrogen bonding, ion-dipole and hydrophobic interactions | Not reported | 112.2 nm, GSH-responsive disassembly | Not reported | None | Chemo–photodynamic combination therapy | Fig. 29a | [261] |
| Spherical morphology | Hydrogen bonding, ion-dipole and hydrophobic interactions | Not reported | 141.8 nm, stable | Not reported | None | Combined chemotherapy and O2-economized PDT | Fig. 29d | [262] |
| Not reported | Ion-dipole and hydrophobic interactions | Not reported | 250 nm, good photostability | None | 24.4% | In situ bacteria-responsive NIR PTT | Fig. 30 | [263] |
Table 9. Summary of porphyrins self-assembly via host–guest interactions with calix[n]arenes and pillar[n]arenes for phototherapy.
| Type of Macrocycles | Morphology | Supramolecular interactions | Content of porphyrin | Size and stability | Yield of ROS | PCE | Applications | Figs | Refs. |
|---|
| Calix[n]arenes | Polymeric NPs | Hydrogen bonding, π–π stacking and hydrophilic-hydrophobic interactions | 12% | 139 ± 49 nm, stable | Not reported | None | Host–guest interaction of star-like calix[4]arene and Ce6 for PDT | Fig. 31a | [269] |
| NPs | Hydrogen bonding, π–π stacking and hydrophilic-hydrophobic interactions | Not reported | 115 ± 5 nm, ATP-responsive releasing PSs | Not reported | None | Biomarker displacement activated phototheranostics | Fig. 31b | [270] |
| Pillar[n]arenes | NPs | Electrostatic, π–π stacking, C–H∙∙∙π interactions | Not reported | ∼150 nm, disassembly when pH < 7 | Not reported | None | Mitochondria-targeting PDT | None | [280] |
| NPs | Electrostatic, hydrogen bonding, π–π stacking interactions | Not reported | ∼75 nm, disassembled at acidic condition | Not reported | None | Programming tumor-specific PDT and catalytic therapy | None | [282] |
| Sheet-like aggregates and NPs | Hydrogen bonding, cation–π, hydrophilic-hydrophobic interactions | 65% | ∼135 nm for NPs, thermo-responsive morphology transformation | Not reported | None | Programmable peptide self-assembly for PDT | Fig. 32a | [283] |
| Spherical structures | C–H∙∙∙π, cation–π, hydrophilic-hydrophobic interactions | Not reported | ∼150 nm, stable | Not reported | 32.1% | Synergistic PTT and PDT | Fig. 32b | [284] |
| NPs | Electrostatic and coordination interactions | Not reported | ∼243 nm, pH-triggering dissociation | Not reported | None | pH-triggering PDT | Fig. 33a | [285] |
| Spherical morphology | C–H∙∙∙π, hydrophilic-hydrophobic interactions | Not reported | ∼140 nm, Cys-responsive releasing H2S | Not reported | None | H2S-generating for enhanced PDT antibacterial infection |
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