A graphitic hollow carbon nitride nanosphere as a novel photochemical internalization agent for targeted and stimuli-responsive cancer therapy

Abstract

As a novel technique, photochemical internalization (PCI) has been employed as a new approach to overcome endo/lysosomal restriction, which is one of the main difficulties in both drug and gene delivery. However, the complicated synthesis procedure (usually requiring the self-assembly of polymers, photosensitizers and cargos) and payload specificity greatly limit its further application. In this paper, we employ a highly fluorescent graphitic hollow carbon nitride nanosphere (GHCNS) to simultaneously serve as a PCI photosensitizer, an imaging agent and a drug carrier. The surface modification of GHCNS with multifunctional polysaccharide hyaluronic acid (HA) endows the system with colloidal stability, biocompatibility and cancer cell targeting ability. After CD44 receptor-mediated endocytosis, the nanosystem is embedded in endo/lysosomal vesicles and HA could be specially degraded by hyaluronidase (Hyal), inducing open pores. In the following, with visible light illumination, GHCNS could produce ROS that effectively induced lipid peroxidation and caused endo/lysosomal membrane break, accelerating the cytoplasmic release of the drug in the targeted and irradiated cells. As a result, significantly increased therapeutic potency and specificity against cancer cells could be achieved.

Combating Biofilm Associated Infection In Vivo: Integration of Quorum Sensing Inhibition and Photodynamic Treatment based on Multidrug Delivered Hollow Carbon Nitride Sphere

“…In other words, PDT can be a useful supplementary strategy for QSIs in enhancing bactericidal effect and reducing the possibility of drug resistance. Among lots of PDT agents, nanosized graphitic hollow carbon nitride sphere (HCNS) is expected to be a competent candidate . Since it has a uniform hollow structure and a porous shell with N‐bridged tri‐s‐triazine repeating units, serving as light‐harvesting antennae, enhanced ROS generators and large containers.…”

Rational design of block copolymer self-assemblies in photodynamic therapy

“…This technique allows for a spatiotemporal control of the release of the endosomal content into the cytosol [190]. PCI is applied for the codelivery of a photosensitizer with an active agent such as nucleic acids [191], proteins [192], anticancer agents [193][194][195], or nanoparticles [48,196]. In the area of nanomedicine, this concept may be a powerful tool when associated with nanovectors such as copolymer micelles to increase the efficacy of the drug delivery [168].…”

Trigger-Responsive Gene Transporters for Anticancer Therapy

“…In addition, it destabilizes the endocytic vesicles in cells, allowing the nanoparticle cargo to escape the lysosomal degradation and the photosensitizer (PS) to bind to the cell membrane surface and to be internalized along with the cargo, which later gets released after irradiating the cell with a light source [129]. Furthermore, a PSs should be amphiphilic because they should not penetrate or intercalate with the cellular membranes and should be present in the endosome vesicle surface while internalizing the gene cargo [9,130,131].…”