Tumor Acidity/NIR Controlled Interaction of Transformable Nanoparticle with Biological Systems for Cancer Therapy

Precisely controlling the interaction of nanoparticles with biological systems (nanobio interactions) from the injection site to biological targets shows great potential for biomedical applications. Inspired by the ability of nanoparticles to alter their physicochemical properties according to different stimuli, we explored the tumor acidity and near-infrared (NIR) light activated transformable nanoparticle ^DATAT-NP_IR&DOX. This nanoparticle consists of a tumor acidity-activated TAT [the TAT lysine residues’ amines was modified with 2,3-dimethylmaleic anhydride (DA)], a flexible chain polyphosphoester core coencapsulated a NIR dye IR-780, and DOX (doxorubicin). The physicochemical properties of the nanoparticle can be controlled in a stepwise fashion using tumor acidity and NIR light, resulting in adjustable nanobio interactions. The resulting transformable nanoparticle ^DATAT-NP_IR&DOX efficiently avoids the interaction with mononuclear phagocyte system (MPS) (“stealth” state) due to the masking of the TAT peptide during blood circulation. Once it has accumulated in the tumor tissues, ^DATAT-NP_IR&DOX is reactivated by tumor acidity and transformed into the “recognize” state in order to promote interaction with tumor cells and enhance cellular internalization. Then, this nanoparticle is transformed into “attack” state under NIR irradiation, achieving the supersensitive DOX release from the flexible chain polyphosphoester core in order to increase the DOX–DNA interaction. This concept provides new avenues for the creation of transformable drug delivery systems that have the ability to control nanobio interactions

Acetal-Linked Hyperbranched Polyphosphoester Nanocarriers Loaded with Chlorin e6 for pH-Activatable Photodynamic Therapy

Nanocarrier-mediated photodynamic therapy (PDT), which involves the systemic delivery of photosensitizers (PSs) into tumor tissue and tumor cells, has emerged as an attractive treatment for cancer. However, insufficient PS release limits intracellular cytotoxic reactive oxygen species (ROS) generation, which has become a major obstacle to improving the PDT therapeutic efficacy. Herein, a novel hyperbranched polyphosphoester (hbPPE) containing numerous acetal bonds (S-hbPPE/Ce6) was explored as a chlorin e6 (Ce6) nanocarrier for PDT. S-hbPPE/Ce6 with a branched topological structure efficiently encapsulated Ce6 and then significantly enhanced its internalization by tumor cells. Subsequently, the endo-/lysosomal acid microenvironment rapidly cleaved the acetal linkage of S-hbPPE and destroyed the nanostructure of S-hbPPE/Ce6, resulting in increased Ce6 release and obviously elevated the intracellular ROS generation under illumination. Therefore, treatment with S-hbPPE/Ce6 noticeably enhanced the PDT therapeutic efficacy, indicating that such a pH-sensitive hbPPE nanocarrier has great potential to improve the PDT therapeutic efficacy for cancer therapy

Ultrathin Black Phosphorus Nanosheets for Efficient Singlet Oxygen Generation

Benefiting from its strong oxidizing properties, the singlet oxygen has garnered serious attentions in physical, chemical, as well as biological studies. However, the photosensitizers for the generation of singlet oxygen bear in low quantum yields, lack of long wavelength absorption band, poor biocompatibility, undegradable in living tissues, and so on. Here we first demonstrate the exfoliated black phosphorus nanosheets to be effective photosensitizers for the generation of singlet oxygen with a high quantum yield of about 0.91, rendering their attractive applications in catalysis and photodynamic therapy. Through in vitro and in vivo studies, the water dispersible black phosphorus nanosheets show notable cancer therapy ability. In addition, the photodegradable character of black phosphorus from element to biocompatible phosphorus oxides further highlights its therapeutic potential against cancer. This study will not only expand the breadth of study in black phosphorus but also offer an efficient catalyst and photodynamic therapy agent

ROS-Sensitive Polymeric Nanocarriers with Red Light-Activated Size Shrinkage for Remotely Controlled Drug Release

Drug delivery systems with remotely controlled drug release capability are rather attractive options for cancer therapy. Herein, a reactive oxygen species (ROS)-sensitive polymeric nanocarrier TK-PPE@NP_Ce6/DOX was explored to realize remotely controlled drug release by light-activated size shrinkage. The TK-PPE@NP_Ce6/DOX encapsulating chlorin e6 (Ce6) and doxorubicin (DOX) was self-assembled from an innovative ROS-sensitive polymer TK-PPE with the assistance of an amphiphilic copolymer poly­(ethylene glycol)-<i>b</i>-poly­(ε-caprolactone) (PEG-<i>b</i>-PCL). Under the 660 nm red light irradiation, ROS generated by the encapsulated Ce6 were capable of cleaving the TK linker <i>in situ</i>, which resulted in the rapid degradation of the TK-PPE@NP_Ce6/DOX core. Consequently, the size of TK-PPE@NP_Ce6/DOX shrank from 154 ± 4 nm to 72 ± 3 nm, and such size shrinkage affected further triggered rapid DOX release. As evidenced by both <i>in vitro</i> and <i>in vivo</i> experiments, such ROS-sensitive polymeric nanocarriers with light-induced size shrinkage capability offer remarkable therapeutic effects in cancer treatment. This concept provides new avenues for the development of light-activated drug delivery systems for remotely controlled drug release <i>in vivo</i>