Sequential application of a cytotoxic nanoparticle and a PI3K inhibitor enhances antitumor efficacy

Ambarish Pandey, Ashish Kulkarni, Bhaskar Roy, Aaron Goldman, Sasmit Sarangi, Poulomi Sengupta, Colin Phipps, Jawahar Kopparam, Michael Oh, Sudipta Basu, Mohammad Kohandel, Shiladitya Sengupta

Research output: Contribution to journalArticlepeer-review

30 Scopus citations


Nanomedicines that preferentially deploy cytotoxic agents to tumors and molecular targeted therapeutics that inhibit specific aberrant oncogenic drivers are emerging as the new paradigm for the management of cancer. While combination therapies are a mainstay of cancer chemotherapy, few studies have addressed the combination of nanomedicines and molecular targeted therapeutics. Furthermore, limited knowledge exists on the impact of sequencing of such therapeutics and nanomedicines on the antitumor outcome. Here, we engineered a supramolecular cis-platinum nanoparticle, which induced apoptosis in breast cancer cells but also elicited prosurvival signaling via an EGF receptor/phosphoinositide 3-kinase (PI3K) pathway. A combination of mathematical modeling and in vitro and in vivo validation using a pharmacologic inhibitor of PI3K, PI828, demonstrate that administration of PI828 following treatment with the supramolecular cis-platinum nanoparticle results in enhanced antitumor efficacy in breast cancer as compared with when the sequence is reversed or when the two treatments are administered simultaneously. This study addresses, for the first time, the impact of drug sequencing in the case of a combination of a nanomedicine and a targeted therapeutic. Furthermore, our results indicate that a rational combination of cis-platinum nanoparticles and a PI3K-targeted therapeutic can emerge as a potential therapy for breast cancer.

Original languageEnglish (US)
Pages (from-to)675-685
Number of pages11
JournalCancer research
Issue number3
StatePublished - Feb 1 2014
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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