Targeted nanoparticles for image‐guided treatment of triple‐negative breast cancer: clinical significance and technological advances

Abstract

Effective treatment of triple negative breast cancer (TNBC) with its aggressive tumor biology, highly heterogeneous tumor cells, and poor prognosis requires an integrated therapeutic approach that addresses critical issues in cancer therapy. Multifunctional nanoparticles with the abilities of targeted drug delivery and non-invasive imaging for monitoring drug delivery and responses to therapy, such as theranostic nanoparticles, hold great promise towards the development of novel therapeutic approaches for the treatment of TNBC using a single therapeutic platform. The biological and pathological characteristics of TNBC provide insight into several potential molecular targets for current and future nanoparticle based therapeutics. Extensive tumor stroma, highly proliferative cells, and a high rate of drug-resistance are all barriers that must be appropriately addressed in order for these nanotherapeutic platforms to be effective. Utilization of the enhanced permeability and retention (EPR) effect coupled with active targeting of cell surface receptors expressed by TNBC cells, and tumor associated endothelial cells, stromal fibroblasts and macrophages is likely to overcome such barriers to facilitate more effective drug delivery. An in depth summary of current studies investigating targeted nanoparticles in preclinical TNBC mouse and human xenograft models is presented. This review aims to outline the current status of nanotherapeutic options for TNBC patients, identification of promising molecular targets, challenges associated with the development of targeted nanotherapeutics, the research done by our group as well as others and future perspectives on the nanomedicine field and ways to translate current preclinical studies into the clinic.

Formulation, characterization and evaluation of morusin loaded niosomes for potentiation of anticancer therapy

“…22 Triple negative breast cancers (TNBCs) are cancers that do not express progesterone receptor (PR), estrogen receptor (ER), and the HER2 isoform of epidermal growth factor receptor (EGFR) and hence due to lack of a specic therapeutic target triple negative breast cancers have limited treatment options. 66 Mor-nio was seen to signicantly reduce the cell viability of MDA-MB-453, a triple negative breast cancer line upon treatment. Morusin has been shown to increase expression of pro-apoptotic marker protein Bax, reduce antiapoptotic protein survivin as well as cause cleavage of caspase 9, -3 and PARP in a dose and time dependent manner in triple negative breast cancer cell lines indicating its ability at targeting anti and pro-apoptotic signals that may increase anti-cancer activity.…”

Nanoparticles for imaging and treatment of metastatic breast cancer

“…In recent years, alternative strategies including NP-based therapeutics are being investigated. [78] The efforts on the nanotherapeutics of metastatic TNBC have been mainly focused on conjugation of NPs with specific ligands for targeting of TNBC cells, conjugation of therapeutics and their combinations for effective tumor inhibition, and development of efficient NP formulations for improved pharmacokinetics.…”

Triple-Negative Breast Cancer: A Review of Conventional and Advanced Therapeutic Strategies

“…However, the disadvantage of EPR is that not all tumors possess leaky vasulature. Therefore an adequate analysis of TNBC tumor biomarkers is required to load the nanoparticles with a ligand specialized in the search for receptors overexpressed like CXCR4 (folic acid receptor) [131]. (2) Another approach used by researchers is active transport that is governed by using biomarkers miRNA (microRNA), proteins, antibodies, as well as therapeutic biomolecules such as siRNA and aptamers, discussed below.…”