Direct Intranuclear Anticancer Drug Delivery via Polydimethylsiloxane Nanoparticles: in Vitro and in Vivo Xenograft Studies

Mishra, Gargi ; Bhattacharyya, Souryadeep ; Bhatia, Vipul ; Ateeq, Bushra ; Sharma, Ashutosh ; Sivakumar, Sri (2017) Direct Intranuclear Anticancer Drug Delivery via Polydimethylsiloxane Nanoparticles: in Vitro and in Vivo Xenograft Studies ACS Applied Materials & Interfaces, 9 (40). pp. 34625-34633. ISSN 1944-8244

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Official URL: http://doi.org/10.1021/acsami.7b08806

Related URL: http://dx.doi.org/10.1021/acsami.7b08806

Abstract

Direct delivery of anticancer drugs to nuclei of tumor cells is required to enhance the therapeutic activity, which can be achieved by a nuclear localization signal (NLS) or peptide-decorated nanovehicles. However, NLS/peptide-based approaches may create certain undesirable immunological responses and the utilized synthesis processes are generally labor intensive. To this end, we report ligand-free, enhanced intranuclear delivery of Doxorubicin (Dox) to different cancer cells via porous polydimethylsiloxane (PDMS) nanoparticles (NPs). PDMS NPs were prepared by sacrificial silica template-based approach and Dox was loaded into the pores of PDMS NPs. These Dox-loaded PDMS NPs show enhanced cytotoxicity and reduce the IC50 values by 84 and 54% for HeLa and PC-3, respectively, compared to free Dox. Further, DNA damage in HeLa cells was estimated using comet assay suggesting enhanced DNA damage (72%) with Dox-loaded PDMS NPs as compared to free Dox (12%). The therapeutic efficiency of PDMS-Dox drug delivery system was tested in prostate cancer (PC-3) xenografts in NOD/SCID mice which showed enhanced tumor reduction (∼66%) as compared to free Dox. Taken together, our PDMS-Dox delivery system shows efficient and enhanced transportation of Dox to tumor cells which can be harnessed to develop advanced chemotherapy-based approaches to treat prostate and other cancers.

Item Type:Article
Source:Copyright of this article belongs to American Chemical Society
Keywords:doxorubicin; drug delivery; intranuclear; nuclear localization signal; polydimethylsiloxane; xenografts
ID Code:127257
Deposited On:13 Oct 2022 09:18
Last Modified:13 Oct 2022 09:18

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