Direct Intranuclear Anticancer Drug Delivery via Polydimethylsiloxane Nanoparticles: in Vitro and in Vivo Xenograft Studies.
Gargi MishraSouryadeep BhattacharyyaVipul BhatiaBushra AteeqAshutosh SharmaSri SivakumarPublished in: ACS applied materials & interfaces (2017)
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.
Keyphrases
- drug delivery
- prostate cancer
- dna damage
- cancer therapy
- cell cycle arrest
- radiation therapy
- cell death
- adipose tissue
- squamous cell carcinoma
- dna repair
- radical prostatectomy
- quantum dots
- oxide nanoparticles
- skeletal muscle
- single cell
- signaling pathway
- high resolution
- highly efficient
- mass spectrometry
- pi k akt
- drug induced
- wild type