Molecularly engineered carrier-free co-delivery nanoassembly for self-sensitized photothermal cancer therapy

Abstract

Background Photothermal therapy (PTT) has been extensively investigated as a tumor-localizing therapeutic modality for neoplastic disorders. However, the hyperthermia effect of PTT is greatly restricted by the thermoresistance of tumor cells. Particularly, the compensatory expression of heat shock protein 90 (HSP90) has been found to significantly accelerate the thermal tolerance of tumor cells. Thus, a combination of HSP90 inhibitor and photothermal photosensitizer is expected to significantly enhance antitumor efficacy of PTT through hyperthermia sensitization. However, it remains challenging to precisely co-deliver two or more drugs into tumors. Methods A carrier-free co-delivery nanoassembly of gambogic acid (GA, a HSP90 inhibitor) and DiR is ingeniously fabricated based on a facile and precise molecular co-assembly technique. The assembly mechanisms, photothermal conversion efficiency, laser-triggered drug release, cellular uptake, synergistic cytotoxicity of the nanoassembly are investigated in vitro. Furthermore, the pharmacokinetics, biodistribution and self-enhanced PTT efficacy were explored in vivo. Results The nanoassembly presents multiple advantages throughout the whole drug delivery process, including carrier-free fabrication with good reproducibility, high drug co-loading efficiency with convenient dose adjustment, synchronous co-delivery of DiR and GA with long systemic circulation, as well as self-tracing tumor accumulation with efficient photothermal conversion. As expected, HSP90 inhibition-augmented PTT is observed in a 4T1 tumor BALB/c mice xenograft model. Conclusion Our study provides a novel and facile dual-drug co-assembly strategy for self-sensitized cancer therapy. Graphic abstract

Chidamide stacked in magnetic polypyrrole nano-composites counter thermotolerance and metastasis for visualized cancer photothermal therapy

“…Through the gap of temperature between M + CMPP + group (47.20 ± 0.44 °C) and CMPP + group (46.07 ± 1.10 °C) was small, the potential vital PTT mechanisms of these two groups are different, leading to a prominent photothermal effect for cancer of M + CMPP + group. The mechanism of PTT includes hyperthermia (Odion et al., 2021 ; Granja et al., 2021 ) and thermal ablation (Zhang et al., 2021 ; Shan et al., 2021 ). Therein, hyperthermia refers to the phenomenon that tumor cells necrosis when they are directly exposed to the temperature range from 41 °C to 47 °C.…”

PpIX/IR-820 Dual-Modal Therapeutic Agents for Enhanced PDT/PTT Synergistic Therapy in Cervical Cancer

“…Optical density (OD) was then recorded at 450 nm, and all plates were covered with aluminum foil to protect them from light. Cell viability was determined by comparing the OD values of the treatment and control groups as follows: − where OD treatment , OD control , and OD blank are the ODs recorded for the treatment, control, and blank groups, respectively. Each experiment was performed at least three times.…”

“…Optical density (OD) was then recorded at 450 nm, and all plates were covered with aluminum foil to protect them from light. Cell viability was determined by comparing the OD values of the treatment and control groups as follows: 55…”

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“…It manifests enormous superiorities to identify, track and control infectious diseases, collect clinical feedback on-demand, and provide access to online treatment and advice for patients in remote regions with limited medical resources. 253,254 Meanwhile, as one of the concerns for personalized medicine, the complex platform integration will inevitably result in challenging circumstances in sensitivity, reliability, reproducibility, and durability. Another reason is that the cost of POC devices should be kept affordable.…”