Multifunctionalized biocatalytic P22 nanoreactor for combinatory treatment of ER+ breast cancer

• Published in: Journal of nanobiotechnology Vol. 16; no. 1; pp. 17 - 14
• Main Authors: Chauhan, Kanchan, Hernandez-Meza, Juan M., Rodríguez-Hernández, Ana G., Juarez-Moreno, Karla, Sengar, Prakhar, Vazquez-Duhalt, Rafael
• Format: Journal Article
• Language: English
• Published: London BioMed Central 20.02.2018; BioMed Central Ltd; BMC
• Subjects: Antineoplastic Agents, Hormonal - administration & dosage; Antineoplastic Agents, Hormonal - pharmacology; Bacteriophage P22 - chemistry; Bacteriophage P22 - enzymology; Biocatalysis; Bioreactors; Biotechnology; Breast cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - metabolism; Care and treatment; Cell Survival - drug effects; Chemistry; Chemistry and Materials Science; Cytochrome P-450 Enzyme System - administration & dosage; Cytochrome P-450 Enzyme System - pharmacology; Cytochrome P450; Drug Carriers - chemistry; Drug Delivery Systems; Enzyme Therapy; Female; Humans; MCF-7 Cells; Models, Molecular; Molecular Medicine; Nanotechnology; Photochemotherapy; Photodynamic therapy; Photosensitizing Agents - administration & dosage; Photosensitizing Agents - pharmacology; Reactive oxygen species; Reactive Oxygen Species - metabolism; Receptors, Estrogen - metabolism; Tamoxifen; Tamoxifen - administration & dosage; Tamoxifen - pharmacology; Testing; Virus-like particle; Reactive oxygen species; Virus-like particle; Photodynamic therapy; Tamoxifen; Cytochrome P450
• ISSN: 1477-3155; 1477-3155
• DOI: 10.1186/s12951-018-0345-2

Background Tamoxifen is the standard endocrine therapy for breast cancers, which require metabolic activation by cytochrome P450 enzymes (CYP). However, the lower and variable concentrations of CYP activity at the tumor remain major bottlenecks for the efficient treatment, causing severe side-effects. Combination nanotherapy has gained much recent attention for cancer treatment as it reduces the drug-associated toxicity without affecting the therapeutic response. Results Here we show the modular design of P22 bacteriophage virus-like particles for nanoscale integration of virus-driven enzyme prodrug therapy and photodynamic therapy. These virus capsids carrying CYP activity at the core are decorated with photosensitizer and targeting moiety at the surface for effective combinatory treatment. The estradiol-functionalized nanoparticles are recognized and internalized into ER+ breast tumor cells increasing the intracellular CYP activity and showing the ability to produce reactive oxygen species (ROS) upon UV 365 nm irradiation. The generated ROS in synergy with enzymatic activity drastically enhanced the tamoxifen sensitivity in vitro, strongly inhibiting tumor cells. Conclusions This work clearly demonstrated that the targeted combinatory treatment using multifunctional biocatalytic P22 represents the effective nanotherapeutics for ER+ breast cancer.