Nanotheranostics 2021; 5(2):213-239. doi:10.7150/ntno.54491

Research Paper

Nanotheranostics through Mitochondria-targeted Delivery with Fluorescent Peptidomimetic Nanohybrids for Apoptosis Induction of Brain Cancer Cells

Isadora C. Carvalho, Alexandra A. P. Mansur, Sandhra M. Carvalho, Herman S. Mansur

Center of Nanoscience, Nanotechnology, and Innovation - CeNano2I, Department of Metallurgical and Materials Engineering, Federal University of Minas Gerais - UFMG, Av. Antônio Carlos, 6627 - Belo Horizonte/MG, Brazil.

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Citation:
Carvalho IC, Mansur AAP, Carvalho SM, Mansur HS. Nanotheranostics through Mitochondria-targeted Delivery with Fluorescent Peptidomimetic Nanohybrids for Apoptosis Induction of Brain Cancer Cells. Nanotheranostics 2021; 5(2):213-239. doi:10.7150/ntno.54491. Available from https://www.ntno.org/v05p0213.htm

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Abstract

Overview: Malignant brain tumors remain one of the greatest challenges faced by health professionals and scientists among the utmost lethal forms of cancer. Nanotheranostics can play a pivotal role in developing revolutionary nanoarchitectures with multifunctional and multimodal capabilities to fight cancer. Mitochondria are vital organelles to eukaryotic cells, which have been recognized as a significant target in cancer therapy where, by damaging the mitochondria, it will cause irreparable cell death or apoptosis.

Methods: We designed and produced novel hybrid nanostructures comprising a fluorescent semiconductor core (AgInS2, AIS) and cysteine-modified carboxymethylcellulose (termed thiomer, CMC_Cys) conjugated with mitochondria-targeting peptides (KLA) forming a macromolecular shell for combining bioimaging and for inducing brain cancer cell (U-87 MG) death.

Results: The optical and physicochemical properties of the nanoconjugates demonstrated suitability as photoluminescent nanostructures for cell bioimaging and intracellular tracking. Additionally, the results proved a remarkable killing activity towards glioblastoma cells of cysteine-bearing CMC conjugates coupled with KLA peptides through the half-maximal effective concentration values, approximately 70-fold higher compared to the conjugate analogs without Cys residues. Moreover, these thiomer-based pro-apoptotic drug nanoconjugates displayed higher lethality against U-87 MG cancer cells than doxorubicin, a model drug in chemotherapy, although extremely toxic. Remarkably, these peptidomimetic nanohybrids demonstrated a relative “protective effect” regarding healthy cells while maintaining high killing activity towards malignant brain cells.

Conclusion: These findings pave the way for developing hybrid nanoarchitectures applied as targeted multifunctional platforms for simultaneous imaging and therapy against cancer while minimizing the high systemic toxicity and side-effects of conventional drugs in anticancer chemotherapy.

Keywords: nanoconjugates, fluorescent nanoparticles, dual-functional bioconjugates, cancer nanomedicine, dual-targeted drug delivery