Person:

Kantoff, Philip

Aim: The development of chemoradiation – the concurrent administration of chemotherapy and radiotherapy – has led to significant improvements in local tumor control and survival. However, it is limited by its high toxicity. In this study, we report the development of a novel NP (nanoparticle) therapeutic, ChemoRad NP, which can deliver biologically targeted chemoradiation.

Method: A biodegradable and biocompatible lipid–polymer hybrid NP that is capable of delivering both chemotherapy and radiotherapy was formulated.

Results: Using docetaxel, indium111 and yttrium90 as model drugs, we demonstrated that the ChemoRad NP can encapsulate chemotherapeutics (up to 9% of NP weight) and radiotherapeutics (100 mCi of radioisotope per gram of NP) efficiently and deliver both effectively. Using prostate cancer as a disease model, we demonstrated the targeted delivery of ChemoRad NPs and the higher therapeutic efficacy of ChemoRad NPs.

Conclusion: We believe that the ChemoRad NP represents a new class of therapeutics that holds great potential to improve cancer treatment.

One limitation of current biodegradable polymeric nanoparticles is their inability to effectively encapsulate and sustainably release proteins while maintaining protein bioactivity. Here we report the engineering of a PLGA-polycation nanoparticle platform with core-shell structure as a robust vector for the encapsulation and delivery of proteins and peptides. We demonstrate that the optimized nanoparticles can load high amounts of proteins (>20% of nanoparticles by weight) in aqueous solution by simple mixing via electrostatic interactions without organic solvents, forming nanospheres in seconds with diameter <200 nm. We also investigate the relationship between nanosphere size, surface charge, PLGA-polycation composition, and protein loading. The stable nanosphere complexes contain multiple PLGA-polycation nanoparticles, surrounded by large amounts of protein. This study highlights a novel nanoparticle platform and nanotechnology strategy for the delivery of proteins and other relevant molecules.

Aim: Two unexplored aspects for irinotecan and cisplatin (I&C) combination chemotherapy are (1) actively targeting both drugs to a specific diseased cell type and (2) delivering both drugs on the same vehicle to ensure their synchronized entry into the cell at a well-defined ratio. In this work we report the use of targeted polymeric nanoparticles (NPs) to co-encapsulate and deliver I&C to cancer cells expressing the Prostate Specific Membrane Antigen (PSMA).

Method: We prepared targeted NPs in a single-step by mixing four different precursors inside microfluidic devices.

Results: I&C were encapsulated in 55-nm NPs and showed an 8-fold increase in internalization by PSMA-expressing LNCaP cells compared to non-targeted NPs. NPs co-encapsulating both drugs exhibited strong synergism in LNCaP cells with a combination index of 0.2.

Conclusion: The strategy of co-encapsulating both irinotecan and cisplatin in a single NP targeted to a specific cell type could potentially be used to treat different types of cancer.