Open AccessDirect Intranuclear Anticancer Drug Delivery via Polydimethylsiloxane Nanoparticles: in Vitro and in Vivo Xenograft Studies
Author(s) -
Gargi Mishra,
Souryadeep Bhattacharyya,
Vipul Bhatia,
Bushra Ateeq,
Ashutosh Sharma,
Sri Sivakumar
Publication year - 2017
Publication title -
acs applied materials and interfaces
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.535
H-Index - 228
eISSN - 1944-8252
pISSN - 1944-8244
DOI - 10.1021/acsami.7b08806
Subject(s) - doxorubicin , hela , in vivo , materials science , drug delivery , cytotoxicity , polydimethylsiloxane , doxorubicin hydrochloride , biophysics , cancer cell , in vitro , cancer research , nanotechnology , cancer , chemistry , chemotherapy , biochemistry , biology , microbiology and biotechnology , genetics
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.