Nanococktail Based on Supramolecular Glyco-Assembly for Eradicating Tumors In Vivo

Abstract

The development of robust phototherapeutic strategies for eradicating tumors remains a significant challenge in the transfer of cancer phototherapy to clinical practice. Here, a phototherapeutic nanococktail atovaquone/17-dimethylaminoethylamino-17-demethoxygeldanamycin/glyco-BODIPY (ADB) was developed to enhance photodynamic therapy (PDT) and photothermal therapy (PTT) via alleviation of hypoxia and thermal resistance that was constructed using supramolecular self-assembly of glyco-BODIPY (BODIPY-SS-LAC, BSL-1), hypoxia reliever atovaquone (ATO), and heat shock protein inhibitor 17dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG). Benefiting from a glyco-targeting and glutathione (GSH) responsive units BSL-1, ADB can be rapidly taken up by hepatoma cells, furthermore the loaded ATO and 17-DMAG can be released in original form into the cytoplasm. Using in vitro and in vivo results, it was confirmed that ADB enhanced the synergetic PDT and PTT upon irradiation using 685 nm near-infrared light (NIR) under a hypoxic tumor microenvironment where ATO can reduce O 2 consumption and 17-DMAG can down-regulate HSP90. Moreover, ADB exhibited good biosafety, and tumor eradication in vivo. Hence, this as-developed phototherapeutic nanococktail overcomes the substantial obstacles encountered by phototherapy in tumor treatment and offers a promising approach for the eradication of tumors.

Red fluorescent BODIPY-based nanoparticles for targeted cancer imaging-guided photodynamic therapy

“…40 In this regard, the observed high stability of LaB- X NPs proposes that they are likely to exhibit a zeta potential larger than approximately ±5 mV. The proposed likelihood is supported by recent studies by Feng et al , 41,42 in which BODIPY-based supramolecular assemblies whose surfaces are covered with lactose moieties were shown to exhibit a zeta potential of approximately −25 mV.…”

Unleashing the Potential of Camptothecin: Exploring Innovative Strategies for Structural Modification and Therapeutic Advancements

“…A key feature of 38 is the incorporation of ATO to address limited PDT efficiency caused by tumor hypoxia, which can spur metastasis and recurrence. ATO inhibits mitochondrial oxidative phosphorylation, an oxygen-consuming process, which improves the hypoxic tumor microenvironment, allocating more oxygen to enhance PDT effects …”

“…139 A key feature of 38 is the incorporation of ATO to address limited PDT efficiency caused by tumor hypoxia, which can spur metastasis and recurrence. ATO inhibits mitochondrial oxidative phosphorylation, an oxygenconsuming process, 140 which improves the hypoxic tumor microenvironment, allocating more oxygen to enhance PDT effects. 141 38 demonstrated stability in physiological environments and responsiveness to tumor conditions, with 95% CPT-Py release within 24 h under acidic tumor pH 5.5 versus less than 25% release at pH 7.4.…”

A supramolecular nanoplatform for imaging-guided phototherapies via hypoxia tumour microenvironment remodeling

“…Atovaquone (ATO) as a mitochondrial respiratory inhibitor provided a promising way to tackle the hypoxia problem in the TME. [20][21][22][23] ATO could inhibit mitochondria-associated oxidative phosphorylation (OXPHOS), the proceeding of which contributed to the expense of oxygen. [24][25][26] In this way, the hypoxia TME would be improved and more oxygen could be distributed to PDT, leading to better PDT therapeutic effects.…”