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A supramolecular NIR nanophotosensitizer for dual-modal imaging and ablation of tumors was constructed by loading disulfiram (DSF) into the vesicle from host–guest complex of lactose-capped pillar[5]arene (LacP5) with aza-BODIPY derivative (BSTA).

A three-in-one self-assembled metallo-nanophotosensitizer system (NLCD) was constructed based on the amphiphilic photosensitizer-coordinated self-assembly of Cu2+ with the simultaneous encapsulation of DOX for multimodal synergistic cancer therapy.

A supramolecular nanoprodrug (DOX@GP5⊃Pro-NFA) was constructed based on the host–guest complexation of a chloride channel blocker prodrug (Pro-NFA) and glycosylated pillar[5]arenes (GP5), which could target chemoresistance cancer therapy.

A supramolecular photosensitizer system LAP5⊃NBSPD was constructed based on host–guest interactions between l-arginine-functionalized pillar[5]arene (LAP5) and NBS pyridine derivative (NBSPD) to synergistically enhance cancer therapeutic effectiveness.

Guanyu Chi,* Yinghua Lv,* Shuang Chao,* Chenxi Hou, Yuxin Pei, Zhichao Pei Shaanxi Key Laboratory of Natural Products and Chemical Biology, College of Chemistry and Pharmacy, Northwest A&F University, Yangling, Shaanxi, 712100, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhichao Pei, Shaanxi Key Laboratory of Natural Products and Chemical Biology, College of Chemistry and Pharmacy, Northwest A&F University, Yangling, Shaanxi 712100, People’s Republic of China, Tel/Fax +86 29 8709-2769, Email peizc@nwafu.edu.cnBackground: Multifunctional nanocarriers based on tumor targeting and intracellular monitoring have received much attention and been a subject of intensive study by researchers in recent years. In this study, we report multifunctional glyconanoparticles with activatable near-infrared probes for tumor imaging and targeted drug delivery.Methods: Disulfide-functionalized dicyanomethylene-4H-pyran (DCM-SS-NH2) and amino-functionalized lactose were modified and loaded onto the surfaces of polydopamine nanoparticles (NPs) by Michael addition or Schiff-base reaction as GSH stimulation–responsive fluorescent probes and tumor-targeting moieties, respectively. Doxorubicin (DOX), a model anticancer drug, was loaded onto polydopamine through π–π interactions directly to prepare multifunctional PLDD (PDA@Lac/DCM/DOX) NPs.Results: Experimental results showed that PLDD NPs had been successfully prepared. DCM, the fluorescence of which was quenched in PLDD NPs, was able to restore red fluorescence in a solution with a GSH concentration of 5 mM. The amount of DOX released from PLDD NPs was 44% over 72 hours in a weak-acid environment (pH 5). The results of CLSM and flow cytometry indicated that the PLDD NPs had good HepG2-targeting ability due to the special recognition between lactose derivative of NPs and overexpressed asialoglycoprotein receptors on HepG2 cell membrane. More importantly, the disulfide bond of DCM-SS-NH2 was broken by the high concentration of GSH inside cancer cells, activating the near-infrared fluorescence probe DCM for cancer-cell imaging. MTT assays indicated that PLDD NPs exhibited higher anticancer efficiency for HepG2 cells and had reduced side effects on normal cells compared with free DOX.Conclusion: The fluorescence of modified DCM loaded onto PLDD NPs is able to be restored in the high-concentration GSH environment within cancer cells, while improving the effectiveness of chemotherapy with reduced side effects. It provides a good example of integration of tumor imaging and targeted drug delivery.Keywords: near-infrared probes, targeted drug delivery, GSH-responsive, tumor-cell imaging, polydopamine

The rational integration of chemotherapy and hydroxyl radical (·OH)-mediated chemodynamic therapy (CDT) via functional metal-organic frameworks (MOF) carriers has great potential in cancer therapy. In this work, aminotriazole (3-AT) doped polyhedral metal organic frameworks (denoted as MAF) were prepared by template ligand replacement, where CDT was initiated by Cu2+/Cu+ modulated Fenton reaction and enhanced by effectively regulating the catalase activity with 3-AT. However, a rod-like Cu-MOF with 3-AT served as a ligand was obtained by the hydrothermal method without using template. In contrast to Cu-MOF, pH-responsive MAF was chosen as the carrier for targeted drug delivery due to its higher drug load of 17.6% and relatively uniform size, where doxorubicin (DOX) as a model drug was loaded in its cavity and hyaluronic acid (HA) was coated on its surface via electrostatic interactions (denoted as HA-MAF@DOX). In vitro experiments demonstrated that HA-MAF@DOX had high transport efficiency of DOX, effective regulation of catalase (CAT) activity and enhanced cytotoxicity to HepG2 cells. This work is the first use of enzyme inhibitors as ligands to construct functional MOFs via template ligand replacement for effective regulating enzyme activity, mediating intracellular redox homeostasis and enhancing CDT efficacy, which provides a feasible strategy for the construction the functional MOFs in cancer therapy.

A novel core-shell metal organic framework (MOF), Cu-MOF@SMON/DOX-HA, was fabricated using 3-amino-1,2,4-triazole (3-AT) and organosilicon for combined chemo-chemodynamic therapy with high drug-loading capacity, pH/GSH dual-responsiveness, and good biocompatibility. The Cu-MOF@SMON/DOX-HA could not only generate reactive oxygen species, but also effectively consume glutathione (GSH) to induce cell ferroptosis. This work involves the modification of organosilicon on the surface of MOFs, which possess good performance in high drug-loading ability and pH/GSH dual-responsive degradation for combined chemo-chemodynamic therapy.

We report a GLUTs/GSH cascade targeting-responsive bioprobe via the coordination of copper ions with a glucose-based coumarin derivative ligand for simple and ultrasensitive detection of circulating tumor cells.

We report a glycol nanomedicine based on a metal-coordination supramolecular self-assembly strategy for targeting drug delivery and release monitoring, as well as synergistic chemo-chemodynamic therapy.

Covalently bridged pillararene-based polymers (CBPPs) are a special class of macrocycle-based polymers in which multiple pillararene monomers are attached to the polymer structures by covalent bonds. Owing to the unique molecular structures including the connection components or the spatial structures, CBPPs have become increasingly popular in applications ranging from environmental science to biomedical science. In this review, CBPPs are divided into three types (linear polymers, grafted polymers, and cross-linked polymers) according to their structural characteristics and described from the perspective of synthesis methods comprehensively. In addition, the applications of CBPPs are presented, including selective adsorption and separation, fluorescence sensing and detection, construction of supramolecular gels, anticancer drug delivery, artificial light-harvesting, catalysis, and others. Finally, the current challenging issues and comprehensive prospects of CBPPs are discussed.

Real-time detection of glycosylation on label-free cancer cell surfaces is of significance for the diagnosis and treatment of cancer. In this work, we have successfully developed a novel dynamic reversible sensor based on pH-sensitive phenylboronic esters to determine in real-time the binding kinetics of protein-carbohydrate interactions on suspension cancer cell surfaces using a quartz crystal microbalance (QCM) technique.

A disulfide-induced supra-amphiphilic co-assembly strategy for hydrophobic drug co-delivery in combination therapies was proposed based on a disulfide bond containing hydrophobic pro-drug-photosensitizer (BG) and a hydrophilic/targeting dimer lactose molecule (Lac-SS-Lac). The anti-tumor efficiency was significantly enhanced by the combination therapies of epidermal growth factor receptor (EGFR) targeted therapy and phototherapy in EGFR-positive and/or galectin overexpressed tumors.

A supramolecular nano-delivery system GP5⊃Pro-ANI based on the host-guest complex of glycosylated pillar[5]arene (GP5) and an amide linked fluorescent PARP inhibitor (4-amino-1,8-naphthimide, ANI) was constructed. The PARP inhibitor ANI, capable of inhibiting the ability of DNA damage repair, was modified into an AIE prodrug (Pro-ANI), which allows for the visualization of real-time cancer cellular drug uptake tracing and selective drug release.

That sulfide anions (S

Platelet factor 4 (PF4) or the CXC chemokine CXCL4 is the most abundant protein within the α-granules of platelets. Previous studies found that PF4 regulates infections of several viruses, including HIV-1, H1N1, hepatitis C virus (HCV), and dengue virus. Here, we show that PF4 is an inhibitor of enterovirus A71 (EV71) and coxsackievirus A16 (CA16) infections. The secreted form of PF4 from transfected cells or soluble purified PF4 from Escherichia coli, even lacking signal peptide affected secretion, obviously inhibited the propagation of EV71 and CA16. Mechanistically, we demonstrated that PF4 blocked the entry of the virus into the host cells by interactions with VP3 proteins of EV71/CA16 and the interaction with SCARB2 receptor-mediated EV71 and CA16 endocytosis. As expected, the incubation of anti-PF4 antibody with PF4 blocked PF4 inhibition on EV71 and CA16 infections further supported the above conclusion. Importantly, pretreatment of EV71 viruses with PF4 significantly protected the neonatal mice from EV71 lethal challenge and promoted the survival rate of infected mice. PF4 derived from natural platelets by EV71/CA16 activation also presented strong inhibition on EV71 and CA16. In summary, our study identified a new host factor against EV71 and CA16 infections, providing a novel strategy for EV71 and CA16 treatment. IMPORTANCE The virus's life cycle starts with binding to cell surface receptors, resulting in receptor-mediated endocytosis. Targeting the entry of the virus into target cells is an effective strategy to develop a novel drug. EV71 and CA16 are the major pathogens that cause hand, foot, and mouth disease (HFMD) outbreaks worldwide since 2008. However, the treatment of EV71 and CA16 infections is mainly symptomatic because there is no approved drug. Therefore, the underlying pathogenesis of EV71/CA16 and the interaction between host-EV71/CA16 need to be further investigated to develop an inhibitor. Here, we identified PF4 as a potent entry inhibitor of EV71 and CA16 via binding to VP3 proteins of EV71 and CA16 or binding to receptor SCARB2. In the EV71 infection model, PF4 protected mice from EV71 lethal challenge and promoted the survival rate of EV71-infected mice. Our study suggests that PF4 represents a potential candidate host factor for anti-EV71 and CA16 infections.

The development of robust phototherapeutic strategies for eradicating tumors remains a significant challenge in the transfer of cancer phototherapy to clinical practice. Here, a phototherapeutic nanococktail atovaquone/17-dimethylaminoethylamino-17-demethoxygeldanamycin/glyco-BODIPY (ADB) was developed to enhance photodynamic therapy (PDT) and photothermal therapy (PTT) via alleviation of hypoxia and thermal resistance that was constructed using supramolecular self-assembly of glyco-BODIPY (BODIPY-SS-LAC, BSL-1), hypoxia reliever atovaquone (ATO), and heat shock protein inhibitor 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG). Benefiting from a glyco-targeting and glutathione (GSH) responsive units BSL-1, ADB can be rapidly taken up by hepatoma cells, furthermore the loaded ATO and 17-DMAG can be released in original form into the cytoplasm. Using in vitro and in vivo results, it was confirmed that ADB enhanced the synergetic PDT and PTT upon irradiation using 685 nm near-infrared light (NIR) under a hypoxic tumor microenvironment where ATO can reduce O2 consumption and 17-DMAG can down-regulate HSP90. Moreover, ADB exhibited good biosafety, and tumor eradication in vivo. Hence, this as-developed phototherapeutic nanococktail overcomes the substantial obstacles encountered by phototherapy in tumor treatment and offers a promising approach for the eradication of tumors.

A galactose-targeting supramolecular photosensitizer system DOX@GP5⊃NBSPD was constructed based on a host-guest inclusion complex. The supramolecular system could achieve efficient delivery of DOX/NBS and selective release under GSH stimulation. In vitro studies revealed that this supramolecular DOX/NBS co-delivery system exhibited high ROS production and excellent cancer cell damage capability in a hypoxic environment. This strategy can therefore achieve enhanced hypoxic-tumor therapeutic effectiveness by chemo-photodynamic combination.

Chenxi Hou,1,* Ning Ma,1,* Ziyan Shen,1 Guanyu Chi,1 Shuang Chao,1 Yuxin Pei,1 Lan Chen,2 Yuchao Lu,2 Zhichao Pei1 1Shaanxi Key Laboratory of Natural Products & Chemical Biology, College of Chemistry and Pharmacy, Northwest A&F University, Yangling, Shaanxi 712100, People’s Republic of China; 2Analysis Center of College of Science & Technology, Hebei Agricultural University, Huanghua, Hebei 061100, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhichao Pei; Yuchao Lu Tel +86 29 87091196Fax +86 29 87092769Email peizc@nwafu.edu.cn; luyuchao@hebau.edu.cnBackground: Conventional chemotherapy using small molecular antitumor drugs suffers from several limitations, for instance poor water solubility, high toxicity, and lack of specificity. However, prodrugs constructed by covalent modification of anticancer drugs can overcome these limitations, which are able to release its active form after entering the tumor tissues by specific stimulus response.Methods: A GSH-responsive glyco-nanoprodrug system has been constructed by self-assembled of amphiphilic lactosemodified camptothecin prodrug molecular (Lac-SS-CPT) for targeting drug delivery and combination therapy.Results: Using HL7702 cells as experimental models, the cytotoxic effects of Lac-SS-CPT were investigated to 10– 30 μmol/L for 48 hours. Notably, the cell viability of Lac-SS-CPT to HL7702 cells was higher compared with free CPT which indicated that Lac-SS-CPT can reduce side-effects. Simultaneously, we have evaluated the anticancer efficiency of doxorubicin hydrochloride (DOX)-loaded Lac-SS-CPT glyco-nanoprodrug system (Lac-SS-CPT@DOX), where Lac-SS-CPT@DOX and free DOX incubated with HpeG2 cells and HL7702 cells for 24, 48, and 72 hours, respectively. It turned out that Lac-SS-CPT@DOX encapsulated anticancer drug (DOX) could decrease DOX side-effect on HL7702 cells and increase DOX anticancer efficiency. More importantly, the CPT and DOX were released from Lac-SS-CPT@DOX in HepG2 cells where a higher GSH concentration exists. Moreover, combination therapy efficiency was evaluated, where free DOX and Lac-SS-CPT@DOX incubated with DOX-resistance HepG2 cells (HepG2-ADR cells), respectively.Conclusion: The results revealed that the Lac-SS-CPT@DOX could enhance the cytotoxicity of DOX for HepG2-ADR cells and provided a new idea for designing an advanced nano-prodrug system toward combination therapy.Keywords: nanoprodrug, target, GSH-responsive, drug delivery, combination chemotherapy

Supramolecular vesicles are the most popular smart nano-drug delivery systems (SDDs) because of their unique cavities, which have high loading carrying capacity and controlled-release action in response to specific stimuli. These vesicles are constructed from amphiphilic molecules via host-guest complexation, typically with targeted stimuli-responsive units, which are particularly important in biotechnology and biomedicine applications. Amphiphilic pillar[n]arenes, which are novel and functional macrocyclic host molecules, have been widely used to construct supramolecular vesicles because of their intrinsic rigid and symmetrical structure, electron-rich cavities and excellent properties. In this review, we first explain the synthesis of three types of amphiphilic pillar[n]arenes: neutral, anionic and cationic pillar[n]arenes. Second, we examine supramolecular vesicles composed of amphiphilic pillar[n]arenes recently used for the construction of SDDs. In addition, we describe the prospects for multifunctional amphiphilic pillar[n]arenes, particularly their potential in novel applications.

Supramolecular vesicles are the most popular smart nano-drug delivery systems (SDDs) because of their unique cavities, which have high loading carrying capacity and controlled-release action in response to specific stimuli. These vesicles are constructed from amphiphilic molecules via host-guest complexation, typically with targeted stimuli-responsive units, which are particularly important in biotechnology and biomedicine applications. Amphiphilic pillar[n]arenes, which are novel and functional macrocyclic host molecules, have been widely used to construct supramolecular vesicles because of their intrinsic rigid and symmetrical structure, electron-rich cavities and excellent properties. In this review, we first explain the synthesis of three types of amphiphilic pillar[n]arenes: neutral, anionic and cationic pillar[n]arenes. Second, we examine supramolecular vesicles composed of amphiphilic pillar[n]arenes recently used for the construction of SDDs. In addition, we describe the prospects for multifunctional amphiphilic pillar[n]arenes, particularly their potential in novel applications.

The integration of acoustics and microfluidics (termed acoustofluidics) presents a frontier in the engineering of functional micro-/nanomaterials. Acoustofluidic techniques enable active and precise spatiotemporal control of matter, providing great potential for the design of advanced nanosystems with tunable material properties. In this work, we introduce an acoustofluidic approach for engineering multifunctional three-dimensional nanostructure arrays and demonstrate their potential in enrichment and biosensing applications. In particular, our acoustofluidic device integrates an acoustic transducer with a sharp-edge-based acoustofluidic reactor that enables uniform patterning of zinc oxide (ZnO) nanoarrays with customizable lengths, densities, diameters, and other properties. The resulting ZnO nanoarray-coated glass capillaries can rapidly and efficiently capture and enrich biomolecules with sizes ranging from a few nanometers to several hundred nanometers. In order to enable the detection of these biomolecules, silver (Ag) nanoparticles are deposited onto the ZnO nanoarrays, and the integrated ZnO–Ag capillary device functions as a label-free plasmonic biosensing system for surface-enhanced Raman spectroscopy (SERS) based detection of exosomes, DNA oligonucleotides, and E. coli bacteria. The optical sensing enhancement of ZnO–Ag capillary is further validated through finite-difference time-domain (FDTD) simulations. These findings not only provide insights into the engineering of functional micro/nanomaterials using acoustofluidics but also shed light onto the development of portable microanalytical devices for point-of-care applications.

A glycol nanomedicine based on a metal-coordination supramolecular self-assembly strategy of GluCC (a copper complex of glucose modified coumarin derivative) and a chemotherapeutic agent of doxorubicin (DOX) was successfully developed.

A cancer-mitochondria dual-targeting nanoparticle based on lactose and ferrocenium derivatives conjugated polydopamine (PDA@Lac/Fc/Hyp) was constructed, which exhibited cancer-targeting and mitochondria-targeting ability deriving from lactose and ferrocenium derivatives due to the specific carbohydrate-protein interaction and cationic species properties, respectively. Moreover, PDA@Lac/Fc/Hyp showed great biocompatibility and phototherapeutic efficiency. This work displays a good example of constructing cancer-mitochondria dual-targeting nanoparticle for synergistic phototherapy.

Multimodal synergistic therapy has gained increasing attention in cancer treatment to overcome the limitations of monotherapy and achieve high anticancer efficacy. In this study, a synergistic phototherapy and hypoxia-activated chemotherapy nanoplatform based on natural melanin nanoparticles (MPs) loaded with the bioreduction prodrug tirapazamine (TPZ) and decorated with hyaluronic acid (HA) was developed. A self-reporting aggregation-induced emission (AIE)-active photosensitizer (PS) (BATTMN) was linked to the prepared nanoparticles by boronate ester bonds. The MPs and BATTMN-HA played roles as quenchers for PS and cancer targeting/photodynamic moieties, respectively. As a pH sensitive bond, the borate ester bonds between HA and BATTMN are hydrolysed in the acidic cancer environment, thereby separating BATTMN from the nanoparticles and leading to the induction of fluorescence for imaging-guided synergistic phototherapy/hypoxia-activated chemotherapy under dual irradiation. TPZ can be released upon activation by pH, near-infrared (NIR) and hyaluronidase (Hyal). Particularly, the hypoxia-dependent cytotoxicity of TPZ was amplified by oxygen consumption in the tumor intracellular environment induced by the AIE-active PS in photodynamic therapy (PDT). The nanoparticles developed in our research showed favorable photothermal conversion efficiency (η = 37%), desired cytocompatibility, and excellent synergistic therapeutic efficacy. The proposed nanoplatform not only extends the application scope of melanin materials with AIE-active PSs, but also offers useful insights into developing multistimulus as well as multimodal synergistic tumor treatment.

Nitric oxide (NO)-mediated gas therapy (GT) and alkyl radical (R•) therapy (ART) are emerging cancer therapy modes, and multi-mode therapy has been recognized as an attractive strategy for enhancing anti-cancer efficacy. In this work, a thermal-responsive R• initiator 2,2'-azobis[2-(2-imidazolin-2-yl)propane] dihydrochloride (AIBI)-loaded glycol-targeting NO nanogenerator was constructed by first the covalent conjugation of thermal-responsive NO donor of S-nitrosothiols (RSNO) on the surface of mesoporous silica-coated gold nanorods (AuNRs@MSN), then the coating of a supramolecular complex of amino pillar[5]arene (NP5) and galactose derivative (G), and finally the loading of AIBI. The glycol-targeting NO nanogenerator demonstrated specific targeting ability to HepG2 cells owing to the recognition between galactose residues and asialoglycoprotein receptors (ASGPR). Specially, upon 808 nm near-infrared (NIR) irradiation, the AIBI-loaded NO nanogenerator generated hyperthermia to achieve photothermal therapy (PTT), and further GT and ART resulted from the thermal responsiveness of RSNO and AIBI, respectively. In vitro experiments revealed that the AIBI-loaded glyco-targeting NO nanogenerator had good biocompatibility and exhibited effective inhibition to the proliferation of HepG2 cells. This work provides a novel way to supramolecular hybrid drug delivery systems for triple-mode targeting therapy of PTT/GT/ART.

Covalently bridged pillararene-based oligomers (CBPOs) are formed by covalent bonding of pillararene monomers, and they play a critical role in expanding the multi-disciplinary application of pillararenes due to their excellent molecular complexing ability, specially designed geometry and multifunctional linking groups. This article provides a comprehensive review of the synthesis and applications of CBPOs. The design and synthetic strategies of a series of CBPOs (dimers, trimers, tetramers and others) are first introduced. Many CBPOs with multi-cavities and unique geometry are very attractive and efficient building blocks for constructing novel smart supramolecular polymers (SPs) with different topological structures through host–guest interactions. We describe the methods of constructing various SPs based on CBPOs in detail. Furthermore, the extensive applications of CBPOs and CBPO-based SPs in recognition and detection of ions and organic small molecules, selective adsorption and separation, artificial light-harvesting systems, catalysis, drug delivery systems, and others are systematically introduced. Finally, the future challenges and perspectives for CBPOs are also highlighted.

Most carrier-based nano drug delivery systems (nano-DDSs) are subjected to complex preparation or purification processes, metabolic instability and potential systemic toxicity. To overcome these issues, it is urgent to develop a multifunctional carrier-free nano-DDS that can be fabricated by a simple approach for enhanced anticancer efficacy. In this work, the carrier-free supramolecular nanoprodrug (CF SNPD) based on lactose (Lac) functionalized dimeric camptothecin (CPT) was developed, in which Lac and CPT were conjugated by the aromatized thioacetal (ATA, a reactive oxygen species (ROS)-responsive bond). The obtained Lac-ATA-CPT2 prodrug and the photosensitizer Chlorin e6 (Ce6) formed CF SNPD (denoted as Ce6@Lac-ATA-CPT2 NPs) in water by supramolecular self-assembly. The design of dimeric CPT endowed Ce6@Lac-ATA-CPT2 NPs with ultrahigh drug-loading capacity (up to 94%) and excellent stability. The Lac-functionalized CF SNPD displayed active specific targetability to HepG2 cells resulting from the carbohydrate-protein interactions. Furthermore, the fluorescence signal of Ce6 facilitated the precise tracking and localization of Ce6@Lac-ATA-CPT2 NPs within the cell. Meanwhile, the ROS generated by Ce6 not only cleaved ATA linker to trigger on-demand CPT release, but also exhibited a killing effect on tumor cells, enabling synergistic therapy via CPT-mediated chemotherapy (CT) and Ce6-induced photodynamic therapy (PDT). Therefore, the multifunctional CF SNPD may be one of the promising therapeutic options for liver cancer.

Owing to its spatiotemporal selectivity and noninvasive nature, photodynamic therapy (PDT) has become a promising approach for the treatment of cancer. However, the non-targeting capability and the accompanying side effects of PDT as well as the low solubility/stability of photosensitizers (PSs) seriously limit its further development. In recent years, host-guest interaction based supramolecular chemistry has attracted more and more attention benefiting from its distinctive properties to introduce macrocyclic hosts including cyclodextrins (CDs), calix[n]arenes (CAs), cucurbit[n]urils (CBs), pillar[n]arenes (PAs), crown ethers, etc. into supramolecular systems, without multiple synthesis steps and complicated purification processes. In particular, supramolecular PDT systems constructed based on macrocylic hosts and PSs through host-guest interactions provide ideal platforms to overcome the limitations of PDT effectively. In this review, recent achievements made in supramolecular PDT systems based on host-guest interactions are comprehensively overviewed, which are categorized into four sections according to the types of macrocyclic hosts. Furthermore, supramolecular PDT combined with other treatments for synergistic therapy is well elucidated. In addition, challenges and perspectives of new supramolecular PDT systems and their potential clinical application are also discussed at the end of the review.