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Zinc-doped Prussian blue nanoparticles for mutp53-carrying tumor ion interference and photothermal therapy.

ABSTRACT: Quite a great proportion of known tumor cells carry mutation in TP53 gene, expressing mutant p53 proteins (mutp53) missing not only original genome protective activities but also acquiring gain-of-functions that favor tumor progression and impede treatment of cancers. Zinc ions were reported as agents cytocidal to mutp53-carrying cells by recovering p53 normal functions and abrogating mutp53. Meanwhile in a hyperthermia scenario, the function of wild type p53 is required to ablate tumors upon heat treatment hence the effects might be hindered in a mutp53 background. We herein synthesized zinc-doped Prussian blue (ZP) nanoparticles (NPs) to combine Zn²⁺ based and photothermal therapeutic effects. An efficient release of Zn²⁺ in a glutathione-enriched tumor intracellular microenvironment and a prominent photothermal conversion manifested ZP NPs as zinc ion carriers and photothermal agents. Apoptotic death and autophagic mutp53 elimination were found to be induced by ZP NPs in R280K mutp53-containing MDA-MB-231 cells and hyperthermia was rendered to ameliorate the treatment in vitro through further mutp53 elimination and increased cell death. The combinatorial therapeutic effect was also confirmed in vivo in a mouse model. This study might expand zinc delivery carriers and shed a light on potential interplay of hyperthermia and mutp53 degradation in cancer treatment.

SUBMITTER: Jin Q

PROVIDER: S-EPMC9640366 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature

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Zinc-doped Prussian blue nanoparticles for mutp53-carrying tumor ion interference and photothermal therapy.

Jin Quanyi Q Zuo Wenbao W Lin Qian Q Wu Ting T Liu Cong C Liu Nian N Liu Jinxue J Zhu Xuan X

Asian journal of pharmaceutical sciences 20220818 5

Quite a great proportion of known tumor cells carry mutation in TP53 gene, expressing mutant p53 proteins (mutp53) missing not only original genome protective activities but also acquiring gain-of-functions that favor tumor progression and impede treatment of cancers. Zinc ions were reported as agents cytocidal to mutp53-carrying cells by recovering p53 normal functions and abrogating mutp53. Meanwhile in a hyperthermia scenario, the function of wild type p53 is required to ablate tumors upon he ...[more]

PMID: 36382302

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Project description:In vivo tracking of dendritic cell (DC) migration to the lymphatic system is essential for evaluating the outcome of DC-based immunotherapies. Novel multimodal imaging strategies with high analytical performance are urgently needed to supply complementary information about the migration and colonization of DCs. In this study, we designed a bimodal imaging agent, namely Au@Prussian blue-Gd@ovalbumin nanoparticles (APG@OVA NPs), for activating DCs and real-time tracking of DC migration process by magnetic resonance imaging (MRI). Moreover, the distribution of the colonized DCs in the lymphatic system was profiled at the single-cell levels based on surface-enhanced Raman scattering (SERS) technique. Methods: In this strategy, PBs as cyanide (CN)-bridged coordination blocks were assembled onto the gold nanoparticles core to provide SERS signal in the Raman-silent region (1800 and 2800 cm-1), which could avoid background signal interference. The doping Gd3+ located in the lattice of PB enables the MRI ability with high relaxivity of the probe. Ovalbumin, an egg allergen, was used as an antigen to activate DCs due to its immunological properties. The prepared APG@OVA NP agents were used to activate DCs with high efficacy and to track their migration and distribution in vivo through SERS/MR bimodal imaging. Results: The APG@OVA NP agents could not only enable DC activating and labeling, but also achieve real-time monitoring of DC migration in vivo and accurate profiling of DC distribution in the lymphatic system. MR imaging indicated the time-dependent migration of the APG@OVA NP-labeled DCs from the footpad to the sentinel lymph node. The background-free Raman mapping of the lymph node tissue slice demonstrated that the activated DCs have successfully colonized to the sentinel lymph node. Conclusion: Concerning the high activating efficacy, dual complementary imaging readouts, and low biological toxicity, the APG@OVA NPs act as high-performance tracking agents for DC-based immunotherapies.

Dataset Information

Zinc-doped Prussian blue nanoparticles for mutp53-carrying tumor ion interference and photothermal therapy.

Publications

Zinc-doped Prussian blue nanoparticles for mutp53-carrying tumor ion interference and photothermal therapy.

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