Photodynamic Chemotherapy Research Articles

Degradable Calcium Phosphate-Coated Upconversion Nanoparticles for Highly Efficient Chemo-Photodynamic Therapy.

The development of a stimulus-responsive nanosystem provides an effective method for improving the accuracy and efficiency of chemotherapy. Meanwhile, traditional photodynamic therapy (PDT) has been substantially restricted by the low dosage of photosensitizer and limited penetration depth of the ultraviolet (UV) or visible light used for excitation. Here, we designed a smart multifunctional nanoplatform by coating core-shell composite mesoporous silica-encapsulated upconversion nanoparticles and chlorin e6 (Ce6) with degradable calcium phosphate, followed by the loading of doxorubicin (DOX). In our structure, the as-synthesized nanoplatform exhibits high responsiveness to a low pH value and degrades rapidly in the weakly acidic tumor microenvironment, allowing the quick release of loaded DOX in tumor sites. Interestingly, the loaded DOX, whose release depends on the pH value and positively correlates with the calcium-ion concentration, enables drug release to be monitored in real time. Combined with photosensitizer Ce6-induced PDT triggered by an 808 nm near-infrared light, synergistic chemo-photodynamic therapy is achieved, thus leading to a highly efficient anticancer treatment in vitro and in vivo. Importantly, the inherent properties of rare earth ions (Gd3+, Yb3+, and Nd3+) make the nanoplatform possess UCL, MRI, and CT trimode imaging capabilities, thus achieving a multiple imaging modality-guided synergistic therapy.

Intracellular tracking of drug release from pH-sensitive polymeric nanoparticles via FRET for synergistic chemo-photodynamic therapy

BackgroundSynergistic therapy of tumor is a promising way in curing cancer and in order to achieve effective tumor therapy with real-time drug release monitoring, dynamic cellular imaging and antitumor activity.ResultsIn this work, a polymeric nanoparticle with Forster resonance energy transfer (FRET) effect and chemo-photodynamic properties was fabricated as the drug vehicle. An amphiphilic polymer of cyclo(RGDfCSH) (cRGD)-poly(ethylene glycol) (PEG)-Poly(l-histidine) (PH)-poly(ε-caprolactone) (PCL)-Protoporphyrin (Por)-acting as both a photosensitizer for photodynamic therapy (PDT) and absorption of acceptor in FRET was synthesized and self-assembled into polymeric nanoparticles with epirubicin (EPI)-acting as an antitumor drug for chemotherapy and fluorescence of donor in FRET. Spherical EPI-loaded nanoparticles with the average size of 150 ± 2.4 nm was procured with negatively charged surface, pH sensitivity and high drug loading content (14.9 ± 1.5%). The cellular uptake of EPI-loaded cRGD-PEG-PH-PCL-Por was monitored in real time by the FRET effect between EPI and cRGD-PEG-PH-PCL-Por. The polymeric nanoparticles combined PDT and chemotherapy showed significant anticancer activity both in vitro (IC50 = 0.47 μg/mL) and better therapeutic efficacy than that of free EPI in vivo.ConclusionsThis work provided a versatile strategy to fabricate nanoassemblies for intracellular tracking of drug release and synergistic chemo-photodynamic therapy.

Carrier-Free, Dual-Functional Nanorods Via Self-Assembly Of Pure Drug Molecules For Synergistic Chemo-Photodynamic Therapy.

BackgroundThe combination of chemo-photodynamic therapy based on nano-technology has emerged as a preferable and promising measure for synergetic antitumor therapy.PurposeThe aim of this study was expected to overcome most of the safety concerns from nano-carriers and improve the chemo-photodynamic synergistic antitumor efficacy.MethodsHerein, we reported a facile and effective approach based on the self-assembly of chemotherapeutic agent 10-hydroxycamptothecin (HCPT) and photosensitizer chlorin e6 (Ce6) for preparing stably dual-functional nanorods (NRs).ResultsThe chemical thermodynamic parameters obtained from isothermal titration calorimeter (ITC) and the microcosmic configuration snapshots acquired by molecular dynamics (MD) simulations verified that HCPT and Ce6 molecules tended to assemble with each other through various intermolecular forces. The as-prepared HCPT/Ce6 NRs possessed a relatively uniform size of around 165 nm and zeta potential of about −29 mV, together with good stability in aqueous solution and freeze-dried state. In addition, both the extra- and intracellular reactive oxygen species (ROS) generation capacity of the NRs under laser irradiation was significantly enhanced compared with Ce6 injections. Moreover, the dual-functional HCPT/Ce6 NRs exhibited a substantial in vitro/in vivo synergistic antitumor efficacy under laser irradiation due to the integration of the two therapeutic modalities into one drug delivery system. Besides, no obvious hepatic or renal toxicity was observed in the NRs treatment groups.ConclusionTaken together, HCPT/Ce6 NRs demonstrated a powerful efficacy in chemo-photodynamic therapy for breast cancer. Therefore, the carrier-free dual-functional NRs prepared in a facile and effective strategy might give inspiration for the development of combined antitumor therapy.

Acid-sensitive ROS-triggered dextran-based drug delivery system for advanced chemo-photodynamic synergistic therapy.

In order to improve the treatment efficacy and reduce the side effects, the synergistic therapy has been effectively exploited in cancer treatment. Herein, we fabricated a kind of acid-sensitive ROS-triggered dextran-based drug delivery system (DHTD/Zn-TPP) for synergistic therapy, in which chemotherapeutics doxorubicin was conjugated to the dextran backbone via ROS cleavable thioketal conjugates while photosensitizer porphyrin (Zn-TPP) was encapsulated via acid-responsive metallic coordinated interaction. The structure and acid-responsive self-assemble behavior of DHTD/Zn-TPP were measured by 1 H NMR, Fourier transform infrared, dynamic laser scattering, and transmission electron microscopy. Further, the in vivo ROS-triggered DOX release and anticancer efficiency were evaluated toward HeLa cells and MCF-7 cells. All the data obtained verified that DHTD/Zn-TPP had a significantly improved cell growth inhibitory effect with light irritation due to the combined application of photodynamic-chemotherapy.

Magnetic Manganese Oxide Sweetgum-Ball Nanospheres with Large Mesopores Regulate Tumor Microenvironments for Enhanced Tumor Nanotheranostics.

An important objective of cancer nanomedicine is to improve the delivery efficacy of functional agents to solid tumors for effective cancer imaging and therapy. Stimulus-responsive nanoplatforms can target and regulate the tumor microenvironment (TME) for the optimization of cancer theranostics. Here, we developed magnetic manganese oxide sweetgum-ball nanospheres (MMOSs) with large mesopores as tools for improved cancer theranostics. MMOSs contain magnetic iron oxide nanoparticles and mesoporous manganese oxide (MnO2) nanosheets, which are assembled into gumball-like structures on magnetic iron oxides. The large mesopores of MMOSs are suited for cargo loading with chlorin e6 (Ce6) and doxorubicin (DOX), thus producing so-called CD@MMOSs. The core of magnetic iron oxides could achieve magnetic targeting of tumors under a magnetic field (0.25 mT), and the targeted CD@MMOSs may decompose under TME conditions, thereby releasing loaded cargo molecules and reacting with endogenous hydrogen peroxide (H2O2) to generate oxygen (O2) and manganese (II) ions (Mn2+). Investigation in vivo in tumor-bearing mice models showed that the CD@MMOS nanoplatforms achieved TME-responsive cargo release, which might be applied in chemotherapy and photodynamic therapy. A remarkable in vivo synergy of diagnostic and therapeutic functionalities was achieved by the decomposition of CD@MMOSs and coadministration with chemo-photodynamic therapy of tumors using the magnetic targeting mechanism. Thus, the result of this study demonstrates the feasibility of smart nanotheranostics to achieve tumor-specific enhanced combination therapy.

Near-infrared light-triggered degradable hyaluronic acid hydrogel for on-demand drug release and combined chemo-photodynamic therapy

In this study, an injectable and near-infrared (NIR) light-triggered ROS-degradable hyaluronic acid hydrogel platform was developed as localized delivery vehicle for photosensitizer protophorphyrin IX (PpIX) and anticancer drug doxorubicin (DOX), to achieve superior combined chemo-photodynamic therapy with light-tunable on-demand drug release. The in situ-forming hydrogel fabricated readily via the formation of dynamic covalent acylhydrazone bonds could efficiently prevent severe self-quenching effect of water-insoluble PpIX due to the covalent binding, leading to localized enhanced photodynamic therapy (PDT). Moreover, the extensive ROS generated by the hydrogel under NIR light irradiation could not only realize efficient PDT effect, but also cleave the ROS-cleavable small molecule crosslinker, inducing the desirable degradation of hydrogel and subsequent on-demand DOX release for cascaded chemotherapy. The developed versatile hyaluronic acid hydrogels have tunable properties, excellent biocompatibility, biodegradability and exhibit outstanding therapeutic effects in both in vitro cellular experiments and in vivo antitumor studies.

Layer structured LDH_ZnPcG4-FA nanoplatform for targeted and imaging guided chemo-photodynamic therapy mediated by 650 nm light

Designing a phototherapeutic material that simultaneously has target, tumor microenvironment (TME)-response, high-quality imaging and synergistic therapy has attracted much attention in anticancer field. Herein, a novel stimuli-responsive multifunctional nanoplatform has been constructed by inserting folic acid linked ZnPcG4 molecules (ZnPcG4-FA) into layered double hydroxides (LDH) by a facile co-precipitation method. Subsequently, chemotherapeutic drug (doxorubicin hydrochloride, DOX) was loaded on the surface of LDH (named as LDH_ZnPcG4-FA/DOX), which can be released in a controlled and targeted manner with the degradation of LDH in the acidic TME. Upon the 650 nm laser irradiation, this nanoplatform demonstrated excellent anticancer efficiency in vitro and in vivo due to the synergistic chemo-photodynamic therapy derived from the released DOX and ZnPcG4 photosensitizer (PS). Interestingly, the luminescent ZnPcG4-FA in LDH_ZnPcG4-FA/DOX exhibited low fluorescence in a neutral environment, while recovered strong fluorescence with the degradation of LDH and release of DOX in acidic TME, implying its TME-responsive imaging property. Besides, in vivo fluorescence imaging of LDH_ZnPcG4-FA/DOX represent that the nanoplatform has higher selectivity to tumor cells than normal cells. This study contributes to design a kind of smart “all-in-one” nanoplatform to realize imaging guided synergistic therapy.

Pro-Oxidant Drug-Loaded Au/ZnO Hybrid Nanoparticles for Cancer-Specific Chemo-Photodynamic Combination Therapy.

Photodynamic therapy (PDT) is a noninvasive therapeutic strategy involving photosensitizers and external light for the selective destruction of target tumors. Chemo-photodynamic combination therapy has attracted widespread attention to improve the outcome of cancer treatment by PDT only. In this study, light-triggered reactive oxygen species (ROS)-generating, polyethylene glycol (PEG)-coated zinc oxide nanorods (PEG-ZnO NRs) were synthesized and complexed with pro-oxidant piperlongumine (PL) to achieve cancer-targeted chemo-photodynamic combination therapy. It was found that PEG-ZnO NRs considerably increased intracellular ROS under UV light irradiation. The loading of PL to PEG-ZnO NRs further increased the intracellular ROS levels in MCF-7 human breast cancer cells due to efficient intracellular delivery of PL. As a result, PL-loaded PEG-ZnO NRs (PL-PEG-ZnO NRs) exhibited a synergistic anticancer activity under UV irradiation compared to free PL and PEG-ZnO NRs. PEG-ZnO NRs were further modified with Au NPs to enhance their capability of generating ROS under light. Au NP-coated PEG-ZnO NRs (Au/PEG-ZnO NRs) with UV irradiation showed higher ROS quantum yields as compared to PEG-ZnO NRs. As a result, PL-loaded Au/PEG-ZnO NRs (PL-Au/PEG-ZnO NRs) exhibited higher cytotoxicity than PL-PEG-ZnO NRs upon UV irradiation. Moreover, PL-Au/PEG-ZnO NRs showed cancer-specific cytotoxicity in MCF-7 cells due to the cancer-specific apoptosis induced by pro-oxidant PL. This study demonstrates that PL-Au/PEG-ZnO NRs have high potential for efficient and cancer-targeted chemo-photodynamic combination therapy.

Polymer-Upconverting Nanoparticle Hybrid Micelles for Enhanced Synergistic Chemo-Photodynamic Therapy: Effects of Emission-Absorption Spectral Match.

Chemo-photodynamic combined therapy is promising in cancer treatment, although low tissue penetration of visible light for activating photosensitizers (e.g., chlorin e6, Ce6) limited its broad applications. Combination of upcoverting nanoparticles (UCNPs) with the photosensitizers endows us with the possibility to utilize highly tissue penetrable near-infrared light; nevertheless, the mismatch between absorption of common photosensitizers (λabs, mainly red) and emission of UCNPs (λem, mainly green) resulted in low energy utilization and unsatisfied therapeutic efficacy in the current UCNP-PDT (photodymanic therapy) platforms. To resolve this problem, herein, we construct polymer-UCNP hybrid micelles (PUHMs) for codelivery of doxorubicin (DOX) and Ce6, and systemically studied the effects of spectral match between λem of UCNPs and λabs of Ce6 on efficiency of synergistic chemo-photodynamic therapy. Compared with spectrally mismatched PUHMs, the spectrally matched PUHMs can significantly enhance the utilization efficiency of upconverted emission energy to activate the photosensitizers and generate more reactive oxygen species (ROS) for enhanced photodynamic therapy. Meanwhile, as the assembled structure of PUHMs can be destroyed by the oxidation of ROS upon 980 nm laser irradiation because of the hydrophobic-hydrophilic transformation of poly(propylene sulfide) (PPS) segment, the spectrally matched PUHMs triggered faster release of DOX, thus resulting in more effective chemotherapy. As a result, the spectrally matched PUHMs induced more prominent cytotoxicity and superior synergistic therapeutic effect for cancer cells in vitro. Our results demonstrated that such spectrally matched PUHMs provide us with an effective strategy for photodynamic-chemo synergistic therapy.

The potentiated checkpoint blockade immunotherapy by ROS-responsive nanocarrier-mediated cascade chemo-photodynamic therapy

Checkpoint inhibitors, such as anti-PD-1/PD-L1 antibodies, have been proven as a promising type of immunotherapy in a number of cancers, but the relatively low response rates limit their scope of clinical application. Here, we report the use of cascade chemo-photodynamic therapy (chemo-PDT) with reactive oxygen species (ROS)-sensitive lipid-polymer hybrid nanoparticles TKHNP-C/D to potentiate the antitumor efficacy of anti-PD-L1 antibody (aPD-L1). Under light irradiation, TKHNP-C/D not only induced photodynamic therapy (PDT) but also boosted intracellular DOX release via the rapid degradation of its hydrophobic core, promoting an efficient cascade of chemo-PDT to inhibit tumor growth by a single treatment. More importantly, the cascade chemo-PDT could evoke anticancer immune responses and efficiently synergize with aPD-L1 to generate an abscopal effect, which could simultaneously inhibit primary and distant tumor growth.

Bioinspired Peptoid Nanotubes for Targeted Tumor Cell Imaging and Chemo-Photodynamic Therapy.

Substantial progress has been made in applying nanotubes in biomedical applications such as bioimaging and drug delivery due to their unique architecture, characterized by very large internal surface areas and high aspect ratios. However, the biomedical applications of organic nanotubes, especially for those assembled from sequence-defined molecules, are very uncommon. In this paper, the synthesis of two new peptoid nanotubes (PepTs1 and PepTs2) is reported by using sequence-defined and ligand-tagged peptoids as building blocks. These nanotubes are highly robust due to sharing a similar structure to those of nontagged ones, and offer great potential to hold guest molecules for biomedical applications. The findings indicate that peptoid nanotubes loaded with doxorubicin drugs are promising candidates for targeted tumor cell imaging and chemo-photodynamic therapy.

Synthesis and engineering of mesoporous ZnO@HAP heterostructure as a pH-sensitive nano-photosensitizer for chemo-photodynamic therapy of malignant tumor cells

The aim of this study was the synthesis of a platform with an optimum physicochemical property and photocatalytic activity for delivery of a standard chemotherapy drug, doxorubicin (Dox). The mesoporous rod-shaped zinc oxide/hydroxyapatite (ZnO@HAP) heterostructures were successfully fabricated and characterized by XRD, FT-IR, FE-SEM, and EDX, and then the nanocomposites with well-defined properties were selected as a nanocarrier for the delivery of Dox. The drug delivery system was decorated with F127 and folic acid (FA), providing a water-soluble system in aqueous medium and targeting effects against tumor cells, respectively. Afterward, Dox was loaded on the surface of the nanocomposites through a single-emulsion solvent-evaporation method. Drug release assessment revealed that proteases cause the release of Dox under a low pH condition, imitating the intracellular compartments like the lysosomes. Based on the biological studies, Dox&FA.F127.ZnO@HAP exerted the most efficient cytotoxic activity against the tumor cells as it was along with the UVA treating. Moreover, it was found that Dox&FA.F127.ZnO@HAP possesses higher cellular uptake efficiency relative to free Dox, particularly in folate-overexpressed tumor cells through clathrin-mediated endocytic pathway. In addition, co-treatment of the tumor cells with Dox&FA.F127.ZnO@HAP and UVA intensified the production of intracellular ROS and drastically enhanced cellular death with mode of apoptosis.

Small-Sized MOF-Constructed Multifunctional Diagnosis and Therapy Platform for Tumor.

In this article, a type of small-sized metal organic framework (MOF), MIL-101(Fe), as an intelligent delivery system was fabricated to load chemotherapy drug dihydroartemisinin (DHA) and photosensitizer methylene blue (MB). In addition, the Fe ions releasedfrom the MOFs in the tumor environment not only enhanced the curative effect of DHA but also catalyzed H2O2 to release O2, which further improved the photodynamic therapeutic effect of the nanocomposites. The nanocomposites can serve as a T2 magnetic resonance imaging contrast agent at the same time. The polylactic acid (PLA) and polyethylene glycol (PEG) were used to modify the surface of MOFs-MB-DHA to acquire the excellent controllable release of drugs and good biocompatibility to decrease the side effects for normal cells. All the results show remarkably increase of the therapeutic efficiency by synergistic chemo-photodynamic therapy. Thus, a smart multifunctional drug delivery system for diagnosis and therapy based on MOFs-MB-DHA@PLA@PEG was constructed for not only real-time imaging but also chemotherapy and photodynamic synergetic therapy to kill the tumor selectively, showing great potential for conquering the existing barrier in chemo-photodynamic synergetic therapy.

Reactive Oxygen Species Synergistic pH/H2O2-Responsive Poly(l-lactic acid)-block-poly(sodium 4-styrenesulfonate)/Citrate-Fe(III)@ZIF-8 Hybrid Nanocomposites for Controlled Drug Release.

Combination of photodynamic therapy and chemotherapeutic drugs is a promising strategy to achieve enhanced anticancer effect. In this study, a novel reactive oxygen species (ROS) synergistic pH/H2O2-responsive nanocomposite has been prepared from the self-assembly of poly(l-lactic acid)-block-poly(sodium 4-styrenesulfonate) in aqueous solution, followed by addition of ferric citrate (Cit-Fe(III)) through electrostatic interaction and growing ZIF-8 among the surface of the particles. Upon H2O2 and visible light stimuli, efficient ROS such as hydroxyl radicals (•OH) and sulfate radicals (SO4•-) can be generated through the catalyst of Cit-Fe(III). Meanwhile, sulfonate-containing polymeric vesicles are disassembled through oxidization by ROS, and the encapsulated doxorubicin (DOX) will gradually diffuse into the ZIF-8 (one type of metal-organic framework, MOF) channels. The gatekeepers, ZIF-8, will collapse only under low pH condition, and a burst drug release is achieved. In the presence of H2O2 and pH stimuli upon visible light exposure, the prepared DOX-loaded nanocomposite exhibits good selectivity for both generating ROS and releasing drug in tumor cell instead of normal cell. The merits of nanocomposites such as good biocompatibility and especially the synergistic effect of chemo-photodynamic therapy make the material a highly promising candidate for drug delivery system in chemo-photodynamic therapy.

PBPK modeling-based optimization of site-specific chemo-photodynamic therapy with far-red light-activatable paclitaxel prodrug

Photodynamic therapy (PDT) is a clinically approved therapeutic modality to treat certain types of cancers. However, incomplete ablation of tumor is a challenge. Visible and near IR-activatable prodrug, exhibiting the combined effects of PDT and local chemotherapy, showed better efficacy than PDT alone, without systemic side effects. Site-specifically released chemotherapeutic drugs killed cancer cells surviving from rapid PDT damage via bystander effects. Recently, we developed such a paclitaxel (PTX) prodrug that targets folate receptors. The goals of this study were to determine the optimal treatment conditions, based on modeling, for maximum antitumor efficacy in terms of drug-light interval (DLI), and to investigate the impact of rapid PDT effects on the pharmacokinetic (PK) profiles of the released PTX.PK profiles of the prodrug were determined in key organs and a quantitative systems pharmacology (QSP) model was established to simulate PK profiles of the prodrug and the released PTX. Three illumination time points (DLI = 0.5, 9, or 48 h) were selected for the treatment based on the plasma/tumor ratio of the prodrug to achieve V-PDT (vascular targeted-PDT, 0.5 h), C-PDT (cellular targeted-PDT, 48 h), or both V- and C-PDT (9 h).The anti-tumor efficacy of the PTX prodrug was greatly influenced by the DLI. The 9 h DLI group, when both tumor and plasma concentrations of the prodrug were sufficient, showed the best antitumor effect. The clearance of the released PTX from tumor seemed to be largely impacted by blood circulation. Here, QSP modeling was an invaluable tool for rational optimization of the treatment conditions and for a deeper mechanistic understanding of the positive physiological effect of the combination therapy.

Aptamer-assisted superparamagnetic iron oxide nanoparticles as multifunctional drug delivery platform for chemo-photodynamic combination therapy.

Superparamagnetic iron oxide nanoparticles (SPION) were widely employed as targeted drug delivery platform due to their unique magnetic property and effortless surface modification. However, the lack of targeting accuracy has been a big obstacle for SPION used in precise medicine. Herein, the tumor-targeting of SPION was enhanced by the conjugation of an aptamer-hybridized nucleic acid structure. The aptamer modified on the surface of SPION was composed of a double-stranded DNA (dsDNA) and a G-quadruplex DNA (AS1411) structure, which carried a chemical anticancer drug, daunomycin (DNM) and a photosensitizer molecule, namely 5, 10, 15, 20-tetra (phenyl-4-N-methyl-4-pyridyl) porphyrin (TMPyP), respectively. The aptamer-dsDNA conjugated SPION nanocarriers (named Apt-S8@SPION) exhibited good stability in serum and nuclease DNase I. The drug-loaded nanocarriers (TMPyP&DNM&Apt-S8@SPION) have high cellular cytotoxicity to A549 and C26 cells which are represently nucleolin-overexpressing cancer cells. The nucleolin-blocking experiments unambiguously evidenced that the formed nanomedicine could target to the cell surface via the specific AS1411-nucleolin interaction, which increased the efficiency of cell uptake. Meanwhile, the TMPyP&DNM&Apt-S8@SPION nanospheres could produce cytotoxic reactive oxygen species efficiently by irradiation of visible light for establishing a new type of PDT to cancer cells. Therefore, the designed TMPyP&DNM&Apt-S8@SPION nanoparticles have magnetic-aptamer dual targeting and combined chemo-photodynamic therapy, and thus were supposed to be ideal drug delivery vehicles with great potential in the era of precision medicine.

High Co-loading Capacity and Stimuli-Responsive Release Based on Cascade Reaction of Self-Destructive Polymer for Improved Chemo-Photodynamic Therapy.

Photodynamic therapy (PDT) shows a promising synergy with chemotherapy in the therapeutic outcome of malignant cancers. The minimal invasiveness and nonsystemic toxicity are appealing advantages of PDT, but combination with chemotherapy brings in the nonselective toxicity. We designed a polymeric nanoparticle system that contains both a chemotherapeutic agent and a photosensitizer to seek improvement for chemo-photodynamic therapy. First, to address the challenge of efficient co-delivery, polymer-conjugated doxorubicin (PEG-PBC-TKDOX) was synthesized to load photosensitizer chlorin e6 (Ce6). Ce6 is retained with DOX by a π-π stacking interaction, with high loading (41.9 wt %) and the optimal nanoparticle size (50 nm). Second, light given in PDT treatment not only excites Ce6 to produce cytotoxic reactive oxygen species (ROS) but also spatiotemporally activates a cascade reaction to release the loaded drugs. Finally, we report a self-destructive polymeric carrier (PEG-PBC-TKDOX) that depolymerizes its backbone to facilitate drug release upon ROS stimulus. This is achieved by grafting the ROS-sensitive pendant thioketal to aliphatic polycarbonate. When DOX is covalently modified to this polymer via thioketal, target specificity is controlled by light, and off-target delivery toxicity is mostly avoided. An oral squamous cell carcinoma that is clinically relevant to PDT was used as the cancer model. We put forward a polymeric system with improved efficiency for chemo-photodynamic therapy and reduced off-target toxicity.

Targeting peptide-decorated biomimetic lipoproteins improve deep penetration and cancer cells accessibility in solid tumor

The limited penetration of nanoparticles and their poor accessibility to cancer cell fractions in tumor remain essential challenges for effective anticancer therapy. Herein, we designed a targeting peptide-decorated biomimetic lipoprotein (termed as BL-RD) to enable their deep penetration and efficient accessibility to cancer cell fractions in a tumor, thereby improving the combinational chemo-photodynamic therapy of triple negative breast cancer. BL-RD was composed of phospholipids, apolipoprotein A1 mimetic peptide (PK22), targeting peptide-conjugated cytotoxic mertansine (RM) and photodynamic agents of DiIC18(5) (DiD). The counterpart biomimetic lipoprotein system without RM (termed as BL-D) was fabricated as control. Both BL-D and BL-RD were nanometer-sized particles with a mean diameter of less than 30 nm and could be efficiently internalized by cancer cells. After intravenous injection, they can be specifically accumulated at tumor sites. When comparing to the counterpart BL-D, BL-RD displayed superior capability to permeate across the tumor mass, extravasate from tumor vasculature to distant regions and efficiently access the cancer cell fractions in a solid tumor, thus producing noticeable depression of the tumor growth. Taken together, BL-RD can be a promising delivery nanoplatform with prominent tumor-penetrating and cancer cells-accessing capability for effective tumor therapy.

Two-dimensional metal-organic-framework as a unique theranostic nano-platform for nuclear imaging and chemo-photodynamic cancer therapy

Nanoscale metal organic frameworks (NMOFs) with porous structure and inherent biodegradability are attractive nanomedicine platforms. In addition to conventional particulate NMOFs, two-dimensional (2D) NMOFs are emerging as a unique type of NMOFs which however have been relatively less explored for nanomedicine applications. Herein, 2D-NMOFs composed of Zn2+ and tetrakis(4-carboxyphenyl) porphyrin (TCPP) are fabricated and functionalized with polyethylene glycol (PEG). Compared to their particulate counterpart, such 2D-NMOFs show greatly increased drug loading capacity and enhanced light-triggered singlet oxygen production, promising for chemotherapy and photodynamic therapy (PDT), respectively. Utilizing the porphyrin structure of TCPP, our 2D-NMOFs could be labeled with a diagnostic radioisotope, 99mTc, for single photon emission computer tomography (SPECT) imaging, which reveals efficient tumor homing of those 2D-NMOFs upon intravenous injection. While offering a remarkable synergistic in vivo antitumor effect for the combined chemo-PDT, such 2D-NMOFs show efficient biodegradation and rapid renal clearance. Our work presents the great promise of 2D-NMOFs for nanomedicine applications.

Indocyanine green-encapsulated erlotinib modified chitosan nanoparticles for targeted chemo-photodynamic therapy of lung cancer cells

The outcome of application of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in patients with non-small-cell lung cancer (NSCLC) always suffers from acquired drug resistance. Its combination with other therapies has been explored with promising synergistic results. Photodynamic therapy (PDT) is an established treatment modality for NSCLC, but the low tumor selectivity of currently available photosensitizers (PSs) hampered the wide clinical application of PDT. Here, we synthesized erlotinib modified chitosan (ECs) by click coupling and developed ECs/indocyanine green (ICG) self-assembled nanoparticles (GECs) for combined targeted chemo-photodynamic therapy. GECs showed oval-shaped particles with a diameter of 267.5 nm, a zeta potential of −15.2 mV, and considerable photostability. In vitro release experiment showed that erlotinib and ICG could be slowly released from GECs in acidic condition with lysozyme. GECs were capable of generating reactive oxygen species (ROS) for PDT under near-infrared laser irradiation. GECs showed synergistic molecular targeted and photodynamic therapeutic effects in inhibition of cellular growth and induction of apoptosis in NSCLC cells. This study demonstrated that the GECs could be a promising platform by combination of targeted chemo-photodynamic therapy for NSCLC treatment.