Supramolecular assembly boosting the phototherapy performances of BODIPYs-海南省生物材料与医疗器械工程研究中心

Supramolecular assembly boosting the phototherapy performances of BODIPYs

发布时间：2024-07-07 发布者：浏览次数：

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a: College of Chemical and Biological Engineering, Shandong University of Science and Technology, 579 Qianwangang Road, Qingdao 266590, China

b: State Key Laboratory of Fine Chemicals, Frontiers Science Center for Smart Materials, School of Chemical Engineering, Dalian University of Technology, Dalian 116024, China

c: Department of Chemistry, College of Sciences, Northeastern University, Shenyang 110819, China

d: Key Laboratory of Hainan Trauma and Disaster Rescue, Key Laboratory of Haikou Trauma, The First Affiliated Hospital of Hainan Medical University, Hainan Medical University, Haikou 571199, China

e: Shandong Haihua Group Co., Ltd, Weifang 262737, China

Received 22 May 2024, Accepted 23 June 2024, Available online 2 July 2024, Version of Record 2 July 2024.

Coordination Chemistry Reviews

Volume 517, 15 October 2024, 216054

https://doi.org/10.1016/j.ccr.2024.216054

Highlights

•Supramolecular assembly can effectively overcome the limitations of BODIPYs and boosted their phototherapy performances.
•Supramolecular assembly improved the water solubility and biocompatibility of BODIPYs.
•Supramolecular assembly enhanced their penetration into deeper tissues, increased its permeability and retention in tumor environments.
•Supramolecular assembly boosted the yields of reactive oxygen species and photothermal conversion efficiencies of BODIPYs.
•BODIPY-based supramolecular systems are poised to significantly advance and play a growing role in anti-tumor treatments.

Highlights

•Supramolecular assembly can effectively overcome the limitations of BODIPYs and boosted their phototherapy performances.
•Supramolecular assembly improved the water solubility and biocompatibility of BODIPYs.
•Supramolecular assembly enhanced their penetration into deeper tissues, increased its permeability and retention in tumor environments.
•Supramolecular assembly boosted the yields of reactive oxygen species and photothermal conversion efficiencies of BODIPYs.
•BODIPY-based supramolecular systems are poised to significantly advance and play a growing role in anti-tumor treatments.

Introduction

Cancer remains a major global health challenge, causing millions of deaths annually and persistently affecting human lives and wellbeing. Consequently, there is an urgent need to develop more effective anti-cancer therapies. Traditional treatments such as chemotherapy and radiotherapy, while widely applicated, are often limited by substantial systemic toxicity and adverse side effects [1], [2], [3], [4], [5]. In response to these limitations, novel clinical approaches such as photodynamic therapy (PDT) and photothermal therapy (PTT) have gained prominence. These phototherapies offer numerous advantages, including high selectivity, minimal toxic side effects, absence of drug resistance, and potent immune activation, positioning them at the cutting edge of research in chemistry, materials science, and medicine [6], [7], [8], [9], [10], [11]. According to the Jablonski diagram in Fig. 1, photosensitizers (PSs), light, and tissue oxygen are the three key components of PDT applications. PDT operates on the principle of electron or energy transfer from triplet PSs to surrounding oxygen molecules, leading to the generation of reactive oxygen species (ROS). These different ROS types, which include a variety of type I radicals like hydroxyl (•OH) and superoxide (O2−•), or singlet oxygen (1O2, type II), inflict cellular damage primarily through photochemical reactions that induce apoptosis in cancer cells [2], [3], [6], [12], [13], [14], [15]. The effectiveness of PDT hinges on the ability of PSs to generate a high yield of ROS while exhibiting low toxicity in the absence of light (dark toxicity), efficiently penetrating deep tissues, and demonstrating effective accumulation within the tumor site. These attributes are essential for targeting tumor tissues and inhibiting tumor growth when illuminated under specific light wavelengths. Thus, advancing the design and functional capabilities of PSs is crucial for enhancing the therapeutic outcomes of PDT [2], [3], [16], [6], [7], [8]. However, the limitation inherent to singular treatments of PDT is highly oxygen-dependent, especially in hypoxic tumors [17], [18]. Therefore, developing novel treatment modalities is crucial.

Similarly, PTT has become another prevalent phototherapy strategy for cancer treatment, capitalizing on the susceptibility of tumor cells to heat-induced apoptosis [9], [10], [19], [20], [21]. Unlike PDT, PTT does not rely on tissue oxygen and can effectively be carried out in hypoxic conditions. During PTT, photothermal agents (PTAs) absorb light at specific wavelengths and convert this energy into heat through non-radiative relaxation processes from the excited states to ground state, leading to tumor cell apoptosis (Fig. 1) [20], [21], [22], [23]. However, PTT tends to require high-intensity laser irradiation during treatments, since the limited transmission ability of low-intensity laser cannot penetrate deep into the organism, resulting in a lack of effective treatments for internal tumors. Thus, the single treatment of PTT is often difficult to achieve the expected effects. It can be mitigated by synergistic therapies with the other treatment modalities such as PDT or chemotherapy, combining the strengths of them [1], [11], [13], [16], [24].

Among various traditional PSs and PTAs characterized by planar, rigid conjugated structures, such as porphyrins [2], [10], [16], [25], [26], [27], [28], phthalocyanine [8], [29], [30], [31], [32], and perylene bisimide [5], [22], [31], [32], [33], boron dipyrromethene (BODIPY) stands out due to its distinct photochemical and photophysical properties. Since their discovery in 1968, BODIPYs, known for their intense light-absorption capabilities, high fluorescence quantum yields, long triplet excited state lifetimes, ease of functionalization, and excellent photostability, have been extensively explored for applicating in phototherapies [24], [34], [35], [36], [37], [38], [39]. Over the past few decades, the structural functionalization and applications of BODIPYs in both PDT and PTT have been rigorously investigated [3], [24], [40], [41], [42], [43], [44]. However, several inherent challenges hinder the broader application of free BODIPY molecules in PDT and PTT. For instance, their hydrophobicity, stemming from planar and rigid structures, limits their water solubility, which is crucial for biological applications. Additionally, their high fluorescence quantum yields and propensity to aggregate in water diminish their ability to generate ROS, severely impacting their effectiveness in PDT [3], [24], [34], [40], [41]. In this context, we will summarize these issues and highlight the ongoing evolution of BODIPY-based phototherapies for overcoming their limitations for enhanced cancer therapy.

Supramolecular assembly, leveraging non-covalent interactions such as hydrogen bonds, van der Waals forces, π–π interactions, and hydrophobic and hydrophilic interactions, offers an effective pathway to circumvent complex organic synthesis processes. This strategy has facilitated the construction of functional materials and has seen significant advancements over the last several decades [45], [46], [47], [48]. Notably, the rapid progress in supramolecular assembly has introduced innovative approaches to enhance the properties of BODIPYs, addressing their previous limitations. These advancements include improving water solubility and biocompatibility, shifting absorption towards the near-infrared (NIR) region, and increasing tumor accumulation and retention, collectively enhancing the performance of BODIPYs in both PDT and PTT therapies [25], [49], [50], [51], [52], [53]. By employing thoughtful design and functionalization, BODIPYs can be structured into supramolecular assemblies that exhibit red-shifted absorption suitable for deep tissue penetration, alongside enhanced biocompatibility and water solubility. This structural and functional tailoring not only facilitates more efficient tumor targeting but also improves the generation of ROS or heat during therapy, opening up vast prospects in PDT and PTT applications [1], [3], [6], [24], [37], [43], [44]. Fortunately, the facial functionalized structures of BODIPYs makes them ideal candidates as versatile building blocks for supramolecular assemblies. Recent research has made significant strides in enhancing the PDT and PTT efficacies of BODIPYs through supramolecular strategies, as demonstrated by numerous studies in recent years [3], [6], [24], [40], [42], [35], [36], [37]. Despite the breakthroughs of supramolecular assembling strategies significantly improving the performances of BODIPYs in anti-cancer phototherapies, several persisting issues and challenges must be addressed to advance their clinical applications further [24], [50]. To provide more valuable resource for researchers keen on exploring and contributing to this promising field of cancer therapy and facilitate their translation into clinical settings, systematically reviewing the latest advancements and ongoing hurdles in the formation of various BODIPY-based assemblies for single or synergistic therapies of PDT and PTT is crucial.

In this review, we aim to comprehensively summarize the strategies and existing challenges associated with designing and constructing various types of BODIPY-based assemblies for both single and synergistic treatments involving PDT and PTT. The construction of BODIPY-based assemblies has been primarily achieved through the following monomers, polymers or complexes (Table 1, Table 2, Table 3, Table 4, Table 5, Table 6): (1) amphiphilic BODIPY molecules; (2) BODIPY-based metal-coordinated macrocycles and heavy-atom-free cyclic BODIPY arrays; (3) BODIPY-encapsulated amphiphilic polymers; and (4) BODIPY-involved host–guest complexes. Each section of this review delves into the optimal design strategies and functional mechanisms of BODIPY-based assemblies, which are extensively discussed and illustrated through numerous figures (Fig. 2, Fig. 3, Fig. 4, Fig. 5, Fig. 6, Fig. 7, Fig. 8, Fig. 9, Fig. 10, Fig. 11, Fig. 12, Fig. 13, Fig. 14, Fig. 15, Fig. 16, Fig. 17, Fig. 18, Fig. 19, Fig. 20, Fig. 21, Fig. 22, Fig. 23, Fig. 24, Fig. 25, Fig. 26, Fig. 27, Fig. 28, Fig. 29, Fig. 30). Additionally, we provide in-depth insights into the therapeutic effects of selected BODIPY-based assemblies, demonstrated through both in vitro and in vivo experiments. These results are critically assessed to underscore their potential for advancing clinical phototherapy applications. This review is crafted to serve as a timely and essential resource for researchers and clinicians interested in the emerging field of supramolecular phototherapies involving BODIPY assemblies. We hope to foster widespread interest and encourage further innovative studies within the phototherapy domain.

Section snippets

Self-assembly of amphiphilic BODIPYs

Since BODIPY cores are composed of organic aromatic compounds, their planar rigid conjugated structures impose significant limitations on water solubility and hinder their biological applications [3], [73]. By incorporating hydrophilic groups, functionalized BODIPYs with amphiphilic structures can self-assemble into various nanostructures, including nanoparticles (NPs), nano-vesicles, and nano-micelles. These nanostructures open up novel opportunities and provide insightful approaches for

Fig. 2. (I) Schematic illustration of molecular structures of PolyFBODIPY, PSDE and PD, self-assembling NP@PolyFBODIPY, generating ROS, and decomposing to release

PSs. (II) Inhibition of tumor growth on a murine cancer model PDXMDR by NP@PolyFBODIPY. (III) Cell viability of PDCMDR cells incubated with NP@PolyBODIPY and

NP@PolyFBODIPY and exposed to irradiation under normoxic or hypoxic conditions. (IV) Tumor growth inhibition curves upon various treatments. Reproduced with

Fig. 3. (a) (I) Schematic illustration of BODIPY with the capability of enhanced ROS generation, tumor targetability, and renal clearance. (II) Relative tumor volume

of tumor-bearing mice in three groups. (III) Photographs of tumor tissues taken from the different groups of tumor-bearing mice. Reproduced with permission [61].

Wiley-VCH.

Fig. 4. (I) The chemical structure of Gal-OH-BDP and formation of Gal-OH-BDP NPs. (II) Galactose-targeting and (III) NIR-II fluorescence imaging-guided PTT. (IV)

Viabilities of HeLa (top) and HepG2 cells (bottom) by using Gal-OH-BDP NPs. (V) IR thermal images (left) and temperature curves of the tumors against time after

injection with PBS and Gal-OH-BDP NPs (right). (VI) Tumor volume changes of the mice in various groups with Gal-OH-BDP NPs. Reproduced with permission [64].

Fig. 5. (a) (I) Self-assembled Bodiplatin-NPs for synergistic PDT/PTT. (II) Images of 4T1 cells stained by Lysotracker Green DND-26 and Hoechst 33,342 after

incubation with Bodiplatin-NPs. (III) Viability of 4T1 cells treated with Bodiplatin-NPs in the presence or absence of Vc. Reproduced with permission [65]. Copyright

2016, Wiley-VCH. (b) (I) Schematic illustration of self-assembly, tumor-targeted delivery and synergistic PDT/PTT mechanisms of 4-IBMs (Top); TEM imaging and

size distribution of 4-IBMs, self-assembly of 2-IB, 4-IB, and 8-IB (Bottom). (II) Viability of 4T1 tumor cells treated with 2-IBMs, 4-IBMs, and 8-IBMs. (III) Tumor

Fig. 6. (I) Chemical structure of BSL. (II) Schematic representation of lactose-mediated endo-cytosis, intracellular BODIPY release triggered by GSH from NPs selfassembled

by BSL, and synergistic therapies of PDT and PTT. (III) Cell viabilities of HL7702, C2C12, HepG2, HepG2/ADR, and HeLa, in the presence of BSL NPs (top),

and Cell viabilities of HepG2, HepG2/ADR, and HeLa in the presence of BSL NPs under irradiation (bottom). (IV) Tumor volumes of BALB/C nude mice bearing

Fig. 7. (I) Structures of the building blocks and self-assembled triangular metallacycles. (II) Illustration of the cellular uptake of NPs prepared from triangular

metallacycles. (III) CLSM images of HeLa cells after incubation with the ligand and metallacycles (top: BODIPY ligand; middle: triangular metallacycles 1; bottom:

triangular metallacycles 2). (IV) Cytotoxicities of triangular metallacycle 2 and BODIPY ligand against HeLa cells. (V) Cytotoxicities of different formulations against

Fig. 8. (a) (I) Structures of BODIPY ligand and the self-assembled triangular metallacycles. (II) Nanoencapsulation method of preparing NPs by using DSPE-PEGMAL.

(III) Cell viabilities of HEK293 cells (left) and U87 cells (right) after treatments. (IV) Variations of the tumor volume (left), gross appearance of the excised

Academy of Science.

Self-assembly of BODIPY-based metal-coordinated macrocycles

In recent years, a considerable number of studies on metal-coordinated BODIPY-based macrocycles for phototherapies have been reported [93], [94], [102], [103], [104], [105], [106], [107]. The use of metal-coordination driven self-assembly has proven to be an effective strategy for constructing various 2D or 3D supramolecular metal-coordination macrocycles with precisely defined sizes and shapes [31], [108], [109], [110], [111]. The integration of BODIPY units into these metal-coordinated

Fig. 10. (I) The synthesis routes of M1 and Melanin-M1, cellular uptake and Pt(II) release of Melanin-M1. (II) Photothermal toxicity of cisplatin, M1 and Melanin-M1

Springer Nature.

Fig. 11. (a) The synthesis (I), anti-tumor mechanism (II), and in vivo application (III) of Ru1085. (IV) Tumor volume changes of tumor-bearing mice against time. (V)

NIR-II imaging guided tumor diagnosis and therapy. (II) Confocal images of A549 cells incubated with Ru1100 and JC-1 in the absence and presence of irradiation.

Fig. 12. (I) Structure of 3d. (II) Changes in the absorption spectrum of DPBF in the presence of 3d for 1O2 characterization. (III) EPR spectra of 3d for O2􀀀

• characterization. (IV) The decay trace of triplet state of 3d. (V) Cell cytotoxicity of 3d micelles to HeLa cells demonstrated by CCK-8 assay. (VI) Images of acridine orange

(green channel, live cell marker) and propidium iodide (red channel, dead cell marker) co-stained HeLa cells incubated. Reproduced with permission [114].

Fig. 13. (a) (I) NIR-mediated PDT, Car-BDP-TNM construction and molecular structures of Car-BDP, PLA-PEG, and PLA-PEG-FA. Viabilities of 4T1 cells (II) and HeLa

cells (III) by Car-BDP-TNM-mediated PDT under different thickness tissue. (IV) Car-BDP-TNM-mediated PDT in deep tumor. (V) Tumor growth inhibition by Car-BDPTNM

schematic illustration of PDT by RET-BDP-TNM. (II) Cell viabilities after treatments with RET-BDP-TNM and B2-TNM: HeLa cells (left), KP7B cells (middle), and 4T1

Self-assembly of BODIPY-encapsulated polymers

Compared to inorganic or metallic NPs, which have raised significant concerns regarding their potential toxicity to biological tissues [122], [123], [124], encapsulating BODIPYs within polymer components has emerged as a prevalent strategy for PDT, PTT, or combined therapies of PDT and PTT. The resultant polymeric assemblies, which can be tailored in terms of composition, size, and surface properties, are generally non-toxic and degrade readily within organisms over time [7], [75], [125], [126]

Fig. 14. (I) Preparation and self-assembly of PPIAB NPs. (II) O2•􀀀 photogeneration mechanism of PPIAB NPs and its application in hypoxic cancer therapy. (III)

fluorescence images of 4T1 tumor bearing mice after PPIAB NPs injection. (IV) Tumor volume changes against time. ***p < 0.001. (V) Photograph of tumor tissues

Fig. 15. (I) Molecular structure of BDP-5. (II) Schematic illustration of the ISC processes, reduction of ΔES1–T1 for enhancing ISC and increasing 1O2 generation. (III)

Schematic illustration of the self-assembly of BDP-5 NPs. (IV) (left) Fluorescent images of HeLa tumor-bearing mice after injection of BDP-5 NPs or normal saline;

(right) tumor growth curves in HeLa tumor-bearing mice with injection of BDP-5 NPs (blue) or normal saline (black). (V) Cell viabilities of HeLa cells after treatments

Fig. 16. (I) Molecular structures of helical-BDP and ordinary BDP (top) and the side view of the RHF optimized ground structures (bottom). (II) Cell viabilities of

CT26 cells treated with increasing concentrations of helical-BDP-NPs (left) and IRDye 700DX (right). (III) Schematic illustration of helical-BDP-NPs with anti-PD-L1

for tumor treatment. (IV) Primary (left) and artificial metastatic (right) tumor volume growth curves in tumor-bearing mice. Reproduced with permission [142].

Fig. 17. (a) (I) Top: self-assembly of AN-BDP and the intermolecular interaction mode in NPs. Bottom: the AN-BDP-contained NPs for PDT. (II) Cell viability of 4T1

cells treated with AN-BDP NPs. (III) Tumor volume changes of mice bearing tumors at different conditions. *p < 0.05, **p < 0.01, and ***p < 0.001. Reproduced with

Fig. 18. (I) The structure of α,β-linked BODIPYs, the process of generation of O2􀀀 • instead of 1O2, and the application for PDT in vivo. (II) The energy gaps of T1–S0 and

Fig. 19. (I) Schematic illustrations of preparing water-stable nano-J-aggregates (J-NP). (II) The mechanism of PTT performance of J-NP. (III) Molecular structures

(BDP-H and BDP) and BDP J-dimer driven by duple Br–π interactions. (IV) UV–vis absorption spectra of BDP monomer in DMSO (blue) and J-NS NPs in water (red).

Fig. 20. (a) (I) Constructing Nano-BFF and its PTT application. (II) 4T1 cells viabilities administrated with Nano-BFF. Without irradiation (top), under 808 (middle)

and 1064 nm (bottom) laser exposure. (III) Top: temperature variations at tumor site of the mice against time. Middle: relative tumor volumes in different treatment

Royal Society of Chemistry.

Fig. 21. (a) (I) Molecular structures of BDP1, BDP2, BisBDP1, and BisBDP2. (II) Schematic illustrations of the PA imaging–guided PTT by BisBDP2-contained Jaggregates.

(III) Temperature variations at tumor site of the mice against irradiation time. (IV) Relative fluorescence intensity in orthotopic liver tumor of the mice

strategic design of CT-coupled J-aggregates. (II) Cell viabilities of Hepa1-6 and HepG2 cells treated with BDP2-NPs. (III) Tumor growth curves of various groups

Fig. 22. (I) Protonation mechanism of NAB induced by pH changes. (II) Schematic illustration of the radiative and non-radiative transitions induced by pH changes.

(III) Tumor volume changes of different mouse groups. (**p < 0.01). (IV) Schematic illustration of pH-sensitive NAB-contained NPs for PAI and PTI guided synergistic

Fig. 23. (a) (I) Schematic illustration of combined PDT and PTT using BODIPY-contained polymeric vesicles. Viabilities of 4T1 tumor cells treated with BODIPY

and their formation of NPs. (II) Schematic illustration of photoconversion routes of CPs-based NPs. (III) Combined PDT and PTT by utilizing tri-BDP-NPs against

Fig. 24. (I) Schematic illustration of encapsulating BODIPY-Ir for constructing micelles. (II) Photophysical processes of generating 1O2 and photothermal conversion.

(III) Intracellular PDT/PTT treatments for cancer cells apoptosis. (IV) 1O2 quantum yields of Micelle-Ir, BODIPY-Ir and BODIPY-I by using DPBF as 1O2 scavenger. (V)

Fig. 25. (I) Schematic illustration of aromatic ring-fused aza-BODIPYs J-aggregates. (II) JBDP-a NPs used for combined PDT and PTT. (III) Survival rate of 4T1 cells

incubation with JBDP-a NPs or commercial IR-1061 at different concentrations. (IV) The tumor volume of various mice groups under different conditions. Reproduced

Fig. 26. (I) Schematic illustration of the structures of PEG, BODIPY, and prodrug (PTX), the self-assembly and combination therapy processes of NPs with optimized

ratio. (II) Viabilities of cancer cells treated with Ada–BODIPY and Ada–PTX with various ratios. (III) Time-dependent tumor volumes of different mice with different

treatments. (IV) Tumor weights of mice with different treatments. (V) Body weights of the mice after different treatments. Reproduced with permission [198].

Fig. 27. (I) Representation of self-degradable BDP2IPh PS for PDT and chemical structure of BDP2IPh and CB[7]. (II) Decay traces of triplet states for BDP2IPh (left)

and BDP2IPh-CB[7] (right). (III) ADPA as the probe to monitor 1O2 generation abilities of BDP2IPh and BDP2IPh-CB[7]. (IV) MCF-7 cell viabilities with BDP2IPh and

BDP2IPh-CB[7] treatments in various conditions: in darkness (top left) and under light irradiation (top right); safety tests of BDP2IPh residues towards BEAS-2B cells

Self-assembly of BODIPYs via host–guest interactions

Supramolecular host–guest chemistry has gained significant prominence since the Nobel Prize in Chemistry was awarded in 1987 to Pedersen, Cram, and Lehn [194]. Herein, we introduce three primary macrocyclic hosts: cyclodextrin (CD) [195], [196], [197], [198], cucurbituril (CB) [199], [200], [201], [202], [203], and pillar[n]arene [204], [205], [206], [207], [208], subsequently summarize how these macrocycles form supramolecular assemblies with BODIPYs to enhance their PDT and PTT performances.

Fig. 28. (I) Schematic illustration of the fabrication of host–guest complexes (HG) and generation of ROS. (II) Viabilities of HeLa cells subjected to a range of HG

Fig. 29. (I) Schematic illustrations of chemical structures, cartoon representations of P5, BDMI, MI, and CDDP, the preparation of CDDP@Suprasomes,

CDDP@Liposomes, and their anti-tumor process in vivo. (II) The concentration-dependent photothermal effect of suprasomes. (III) 4T1 cells viabilities after different

Fig. 30. (I) Schematic illustrations of the preparation and anti-tumor mechanism of LacP5⊃BSTA@DSF. (II) The images of living mice after injection of LacP5⊃BSTA. (III) Tumor sizes after treatment. (IV) Tumor volume changes during treatment. Reproduced with permission [210]. Copyright 2023, the Royal Society of Chemistry.

Conclusion and outlook

In this review, we have summarized various supramolecular assembly strategies for constructing BODIPY-based assemblies aimed at enhancing their performance in single or synergistic therapies involving PDT and PTT. The primary structures of these assemblies were constructed by amphiphilic BODIPYs, BODIPY-based metal-coordinated macrocycles, heavy-atom-free cyclic BODIPY arrays, BODIPYencapsulated polymers, and BODIPY-based host–guest complexes. Significant advancements have been made in recent years toward enhancing the PDT and PTT capabilities of BODIPYs through supramolecular assembly. This includes improved water solubility, biocompatibility, and penetration depth into tumor tissues via red-shifted NIR absorption. BODIPY-based NPs have demonstrated selective uptake by tumor cells through the EPR effect. Moreover, many NPs possess targeted therapeutic capabilities, which have amplified their therapeutic efficacy. Effective generation of ROS and heat, pivotal for inducing cancer cell death, has been achieved by modulating the intermolecular interactions within BODIPY assemblies. Additionally, several BODIPYs have been structured for synergistic therapies, addressing the limitations associated with singular PDT or PTT treatments. Consequently, BODIPYbased assemblies summarized in this review exhibited great potential for various anti-tumor phototherapies.

Despite these advancements, several challenges still pose significant hurdles for the clinical application of BODIPY-based supramolecular assemblies:

phototherapy should possess high-targeting performance, excellent water solubility and biocompatibility, robust penetration abilities, efficient tumor accumulation via EPR effects, and high ROS or heat generation capabilities. Additionally, they should be stable, not prone to leakage, and should be easily manufactured without complicated synthesis processes. Although challenges persist in the research of their supramolecular assemblies for PDT and PTT, the potential for improvement through strategic design and rational assembly is immense. As research progresses, we envision BODIPY-based assemblies becoming increasingly sophisticated and playing a vital role in antitumor treatments.

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ReviewSupramolecular assembly boosting the phototherapy performances of BODIPYs

Coordination Chemistry Reviews

Highlights

Highlights

Introduction

Section snippets

Self-assembly of amphiphilic BODIPYs

Self-assembly of BODIPY-based metal-coordinated macrocycles

Conclusion and outlook

Review
Supramolecular assembly boosting the phototherapy performances of BODIPYs