Targeting triple‐negative breast cancer with an aptamer‐functionalized nanoformulation: a synergistic treatment that combines photodynamic and bioreductive therapies
Journal
Journal of Nanobiotechnology
Journal Volume
19
Journal Issue
1
Pages
Article number 89
Date Issued
2021
Author(s)
Abstract
Background: Areas of hypoxia are often found in triple-negative breast cancer (TNBC), it is thus more difficult to treat than other types of breast cancer, and may require combination therapies. A new strategy that combined bioreductive therapy with photodynamic therapy (PDT) was developed herein to improve the efficacy of cancer treatment. Our design utilized the characteristics of protoporphyrin IX (PpIX) molecules that reacted and consumed O2 at the tumor site, which led to the production of cytotoxic reactive oxygen species (ROS). The low microenvironmental oxygen levels enabled activation of a bioreductive prodrug, tirapazamine (TPZ), to become a toxic radical. The TPZ radical not only eradicated hypoxic tumor cells, but it also promoted therapeutic efficacy of PDT. Results: To achieve the co-delivery of PpIX and TPZ for advanced breast cancer therapy, thin-shell hollow mesoporous Ia3d silica nanoparticles, designated as MMT-2, was employed herein. This nanocarrier designed to target the human breast cancer cell MDA-MB-231 was functionalized with PpIX and DNA aptamer (LXL-1), and loaded with TPZ, resulting in the formation of TPZ@LXL-1-PpIX-MMT-2 nanoVector. A series of studies confirmed that our nanoVectors (TPZ@LXL-1-PpIX-MMT-2) facilitated in vitro and in vivo targeting, and significantly reduced tumor volume in a xenograft mouse model. Histological analysis also revealed that this nanoVector killed tumor cells in hypoxic regions efficiently. Conclusions: Taken together, the synergism and efficacy of this new therapeutic design was confirmed. Therefore, we concluded that this new therapeutic strategy, which exploited a complementary combination of PpIX and TPZ, functioned well in both normoxia and hypoxia, and is a promising medical procedure for effective treatment of TNBC. [Figure not available: see fulltext.]. ? 2021, The Author(s).
Subjects
Diseases; Oxygen; Silica; Silica nanoparticles; Tumors; Combination therapy; Histological analysis; Human breast cancer cells; Medical procedures; Photodynamic therapy (PDT); Therapeutic efficacy; Therapeutic strategy; Triple-negative breast cancers; Photodynamic therapy
SDGs
Other Subjects
Diseases; Oxygen; Silica; Silica nanoparticles; Tumors; Combination therapy; Histological analysis; Human breast cancer cells; Medical procedures; Photodynamic therapy (PDT); Therapeutic efficacy; Therapeutic strategy; Triple-negative breast cancers; Photodynamic therapy; aptamer; nanocarrier; protoporphyrin; silica nanoparticle; tirapazamine; antineoplastic agent; aptamer; nanoparticle; oxygen; prodrug; reactive oxygen metabolite; silicon dioxide; tirapazamine; animal experiment; animal model; animal tissue; Article; cell hypoxia; cell killing; controlled study; drug delivery system; drug formulation; drug targeting; female; histology; human; human cell; in vitro study; in vivo study; MDA-MB-231 cell line; mouse; newborn; nonhuman; photodynamic therapy; triple negative breast cancer; tumor volume; tumor xenograft; animal; drug effect; drug screening; multimodality cancer therapy; photochemotherapy; procedures; triple negative breast cancer; tumor cell line; tumor hypoxia; Animals; Antineoplastic Agents; Aptamers, Nucleotide; Cell Line, Tumor; Combined Modality Therapy; Female; Humans; Mice; Nanoparticles; Oxygen; Photochemotherapy; Prodrugs; Reactive Oxygen Species; Silicon Dioxide; Tirapazamine; Triple Negative Breast Neoplasms; Tumor Burden; Tumor Hypoxia; Xenograft Model Antitumor Assays
Publisher
BioMed Central Ltd
Type
journal article