A rationally designed photo-chemo core-shell nanomedicine for inhibiting the migration of metastatic breast cancer cells followed by photodynamic killing

A multifunctional core-shell nanomedicine capable of inhibiting the migratory capacity of metastatic cancer cells followed by imparting cytotoxic stress by photodynamic action is reported. Based on in silico design, we have developed a core-shell nanomedicine comprising of ~ 80 nm size poly(lactic-co-glycolic acid) (PLGA) nano-core encapsulating photosensitizer, m-tetra(hydroxyphenyl)chlorin (mTHPC), and ~ 20 nm size albumin nano-shell encapsulating tyrosine kinase inhibitor, Dasatinib, which impair cancer migration. This system was prepared by a sequential process involving electrospray of polymer core and coacervation of protein shell. Cell studies using metastatic breast cancer cells demonstrated disruption of Src kinase involved in the cancer migration by albumin–dasatinib nano-shell and generation of photoactivated oxidative stress by mTHPC-PLGA nano-core. This unique combinatorial photo-chemo nanotherapy resulted synergistic cytotoxicity in ~ 99% of the motility-impaired metastatic cells. This approach of blocking cancer migration followed by photodynamic killing using rationally designed nanomedicine is a promising new strategy against cancer metastasis.From the Clinical EditorA multifunctional core-shell nanomedicine capable of inhibiting metastatic cancer cell migration, in addition to inducing photodynamic effects, is described in this paper. The authors document cytotoxicity in approximately 99% of the studied metastatic breast cancer cells. Similar approaches would be a very welcome addition to the treatment protocols of advanced metastatic breast cancer and other types of neoplasms.

Graphical AbstractA photo-chemo core-shell nanomedicine with size ~ 100 nm was in silico designed, and developed wherein small molecule loaded protein nano-shell inhibits cancer cell migration, and upon laser irradiation, photosensitizer loaded polymer nano-core exerts cytotoxic ROS, thereby producing ~ 99% synergistic cytotoxicity in the motility-impaired metastatic cells. The computationally optimized core-shell nanomedicine demonstrates its potential for delivering two different anti-tumor drugs to tackle a key mechanism of metastatic cancer together with imparting cytotoxic stress.Figure optionsDownload high-quality image (187 K)Download as PowerPoint slide