A Self-Reinforcing Nanoplatform for Highly Effective Synergistic Targeted Combination Calcium-Overload and Photodynamic Therapy of Cancer.
Dongdong GuoXiaoyong DaiKewei LiuYuhong LiuJiamin WuKun WangShengwei JiangFen SunLijun WangBing GuoDongye YangLaiqiang HuangPublished in: Advanced healthcare materials (2023)
While calcium-overload-mediated therapy (COMT) is a promising but largely untapped therapeutic strategy, combinatory therapy greatly boosts treatment outcomes with integrated merits of different therapies. Herein, BPQD@CaO 2 -PEG-GPC3Ab nanoplatform is formulated by integrating calcium peroxide (CaO 2 ) and black phosphorus quantum dot (BPQD, photosensitizer) with active-targeting glypican-3 antibody (GPC3Ab), for combinatory photodynamic therapy (PDT) and COMT in response to acidic pH and near-infrared (NIR) light, wherein CaO 2 serves as the reservoir of calcium ion (Ca 2+ ) and hydrogen peroxide (H 2 O 2 ). Navigated by GPC3Ab to tumor cells at acidic pH, the nanoparticle disassembles to CaO 2 and BPQD; CaO 2 produces COMT Ca 2+ and H 2 O 2 , while H 2 O 2 makes oxygen (O 2 ) to promote PDT; under NIR irradiation BPQD facilitates not only the conversion of O 2 to singlet oxygen ( 1 O 2 ) for PDT, but also the moderate hyperthermia to accelerate NP dissociation to CaO 2 and BPQD, and conversions of CaO 2 to Ca 2+ and H 2 O 2 , and H 2 O 2 to O 2 , to enhance both COMT and PDT. After supplementary ionomycin treatment to induce intracellular Ca 2+ bursts, the multimodal therapeutics strikingly induces hepatocellular carcinoma apoptosis, likely through activation of the calpains and caspases 12, 9, and 3, up-regulation of Bax and down-regulation of Bcl-2 proteins. This nanoplatform enables a mutually-amplifying and self-reinforcing synergistic therapy. This article is protected by copyright. All rights reserved.
Keyphrases
- photodynamic therapy
- fluorescence imaging
- hydrogen peroxide
- cancer therapy
- drug delivery
- oxidative stress
- nitric oxide
- protein kinase
- squamous cell carcinoma
- small molecule
- stem cells
- cell death
- cell cycle arrest
- radiation therapy
- papillary thyroid
- bone marrow
- reactive oxygen species
- pain management
- fluorescent probe
- smoking cessation
- cell therapy