Surface-Charge-Switchable Nanoclusters for Magnetic Resonance Imaging-Guided and Glutathione Depletion-Enhanced Photodynamic Therapy

Abstract

Photodynamic therapy (PDT) is an effective noninvasive therapeutic method that employs photosensitizers (PSs) converting oxygen to highly cytotoxic singlet oxygen ( 1 O 2 ) under light irradiation. The conventional PDT efficacy is, however, compromised by the nonspecific delivery of PSs to tumor tissue, the hypoxic tumor microenvironment, and the reduction of generated 1 O 2 by the intracellular antioxidant glutathione (GSH). Herein, an intelligent multifunctional synergistic nanoplatform (CMGCC) for T 1 -weighted magnetic resonance (MR) imaging-guided enhanced PDT is presented, which consists of nanoparticles composed of catalase (CAT) and manganese dioxide (MnO 2 ) that are integrated within chlorin-e6-modified glycol chitosan (GC) polymeric micelles. In this system, (1) GC polymers with pH-sensitive surface charge switchability from neutral to positive could improve the PS accumulation within the tumor region, (2) CAT could effectively reoxygenate the hypoxic tumor via catalyzing endogenous hydrogen peroxide to O 2 , and (3) MnO 2 could consume the intracellular GSH while simultaneously producing Mn 2+ as a contrast agent for T 1 -weighted MR imaging. The CMGCC particles possess uniform size distribution, well-defined structure, favorable enzyme activity, and superior 1 O 2 generation ability. Both in vitro and in vivo experiments demonstrate that the CMGCC exhibit significantly enhanced PDT efficacy toward HeLa cells and subcutaneous HeLa tumors. Our study thereby demonstrates this to be a promising synergistic theranostic nanoplatform with highly efficient PDT performance for cancer therapy.

An update in clinical utilization of photodynamic therapy for lung cancer

“…The choice of optimal combinations of photosensitizers, light sources, and treatment parameters are crucial for effective PDT 42 , 43 . The type of photosensitizer used, oxygen concentration within target tumor cells, a dose of light applied, and concentration of photosensitizer uptaken by cancer cells determine the cancer treatment efficacy of PDT 44 - 47 . PDT components can directly induce cellular damage to organelles and cell membranes, depending on where they are generated 21 , 22 .…”

Dendrimer-decorated nanogels: Efficient nanocarriers for biodistribution in vivo and chemotherapy of ovarian carcinoma

“…A 3D cross-linked polymer colloids, nanogels (NGs) as nanocarriers have attracted much attention in biomedical applications, including drug/enzyme delivery, images and therapy of tumors, due to their unique properties [ [14] , [15] , [16] ]. All the time we explored various NGs that having the controllable size, deformable softness, highly porous network, excellent biocompatibility and stimuli-responsiveness can be employed as functional nanocarriers for improved tumor theranostics [ [17] , [18] , [19] , [20] , [21] , [22] , [23] , [24] , [25] ]. In particular, the biocompatible PVCL-based NGs exist a volume phase transition temperature (VPTT) of about 35 °C which is close to body temperature, and high cargo loading capacity along with enhanced tumor accumulation for biomedical purposes [ [26] , [27] , [28] ].…”

Metal‐Coordinated Supramolecular Self‐Assemblies for Cancer Theranostics

“…In addition to the abovementioned works, other studies report the utilization of Mn coordination for the synthesis of nanomedicines to achieve theranostic goals. [ 117 ]…”