Targeted Self‐assembly of Renal Clearable Cu_2‐xSe to Induce Lysosome Swelling for Multimodal Imaging Guided Photothermal/Chemodynamic Synergistic Therapy

Abstract

Renal clearance is critical for nanodrug to avoid the long‐term body retention‐related side effects, while it is difficult to achieve efficient tumor accumulation and retention. The over‐developed lysosomes in cancer cells have become an emerging target for more precise and effective cancer therapy. Herein, a pH‐responsive reversible self‐assembled Cu2‐xSe‐BSA, which can be renal cleared under neutral or basic conditions, is developed for selectively targeted aggregation in cancer lysosomes with enhanced tumor accumulation and retention. Moreover, the aggregation of Cu2‐xSe‐BSA can enhance the photoacoustic imaging signal, photothermal therapy, and chemodynamic therapy capability. Cu2‐xSe‐BSA accumulated in lysosomes cannot only induce lysosomes swelling, but also generate reactive oxygen species in situ, causing lysosomal membrane permeabilization and finally lysosomal cell death. Notably, the assembled Cu2‐xSe‐BSA can dissociate to be renal clearable after the treatments are completed and left the acid tumor microenvironment, being of great significance both in scientific research and clinical trial.

Aggregation-Enhanced Photophysical Performance of D-π-A Structured Hemicyanine for NIR-II Fluorescent and Photoacoustic Imaging-Guided Photothermal Therapy

“…The introduction of aggregation-induced emission groups, such as triphenylamine, tetraphenylethylene, etc. can increase the fluorescence quantum yield and avoid fluorescence quenching. , The surface modification of tumor-targeting probes, such as folic acid, bovine serum albumin, and tumor cell membrane could improve the tumor-targeting capability. − While the couplling of quaternary ammonium or morpholine groups can improve the suborganelles targeting ability. − These strategies may provide some thoughts for designing high efficient molecules for cancer treatment.…”

Photothermal Nanomaterials: A Powerful Light-to-Heat Converter

“…The clinical progresses of PTT with various photothermal nanomaterials have been widely made for the treatment of head and neck cancer, coronary atherosclerosis, diabetic macular abnormalities, age-related macular degeneration, prostate cancer, and genitourinary syndrome of menopause (national clinical trials: NCT 00848042, NCT 01270139, NCT 01975103, NCT 02569892, NCT 02680535, NCT 03288883). , A single-treatment clinical device study of AuroLase Therapy for the direct focal ablation of prostate tissue was demonstrated by the company of Nanospectra Biosciences . Since silica-cored Au nanoshells served as the first photothermal nanomaterials for clinical use, more and more inorganic agents with strong absorption in the NIR region, high chemical stability, adjustable water solubility, and minimal cytotoxicity have entered clinical trials. , Clinical trials have also been underway for small organic molecules due to their good biodegradability, good repeatability, and simple preparation. , Nevertheless, the major challenges for the clinical implementation of photothermal nanomaterials are the complex metabolism and excretion behaviors . The representative works on PTT with diverse photothermal nanomaterials in recent years − are summarized in Table .…”

“…648,653 Clinical trials have also been underway for small organic molecules due to their good biodegradability, good repeatability, and simple preparation. 690,713 Nevertheless, the major challenges for the clinical implementation of photothermal nanomaterials are the complex metabolism and excretion behaviors. 719 The repre- sentative works on PTT with diverse photothermal nanomaterials in recent years 656−706 are summarized in Table 3.…”

“…The combination partners can mutually not only improve the penetration depth of PTT but also augment the antitumor efficacy at lower doses of photothermal agents or lower irradiation laser powers. A number of therapies, such as photodynamic therapy, chemotherapy, radiotherapy, immunotherapy, sonodynamic therapy, chemodynamic therapy, and gene therapy (GT), have been widely incorporated with PTT. ,− For example, as the essential therapeutic approach for malignant tumors, conventional chemotherapy often suffers from low drug release, limited dosage, and heavy systemic toxicity . The combination of photothermal nanomaterials and chemotherapeutic drugs has been utilized to address the mentioned limitations. , Uniform Au@poly­(acrylic acid) (PAA) nanostructures have been facilely synthesized for actively targeted chemo-PTT (Figure a) .…”

In Situ Transformable Pro-nanotheranostic Platform for Activable Photoacoustic Imaging and Synergistic Photothermal/Chemodynamic Cancer Therapy

“…However, very few in situ transformable pro-nanotheranostic agents have been designed based on ion exchange reactions due to the lack of reactions that can take place rapidly and efficiently in mild but complex physiological conditions. It is recognized that the reaction between copper ions and chalcogenide ions is spontaneously ascribed to the small solubility product constants, and the resulting copper chalcogenide nanomaterials exhibit near-infrared (NIR) absorption, − which could potentially be utilized for designing pro-nanotheranostic agents. Indeed, the anion exchange reaction between Cu 2 O nanoparticles and endogenous H 2 S has been engineered for colon cancer theranostics .…”