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Updated: Nov 6, 2025
Polymalic Acid-based Nano Biopolymers for Targeting of Multiple Tumor Markers: An Opportunity for Personalized Medicine?
Published on: June 13, 2014
Targeted polymeric nanoparticles for drug delivery to hypoxic, triple-negative breast tumors
Babak Mamnoon1, Jagadish Loganathan1, Matthew I Confeld1
1Department of Pharmaceutical Sciences, North Dakota State University, Fargo, North Dakota 58102, United States.
Abstract:
High recurrence and metastasis to vital organs are the major characteristics of triple-negative breast cancer (TNBC). Low vascular oxygen tension promotes resistance to chemo- and radiation therapy. Neuropilin-1 (NRP-1) receptor is highly expressed on TNBC cells. The tumor-penetrating iRGD peptide interacts with the NRP-1 receptor, triggers endocytosis and transcytosis, and facilitates penetration. Herein, we synthesized a hypoxia-responsive diblock PLA-diazobenzene-PEG copolymer and prepared self-assembled hypoxia-responsive polymersomes (Ps) in an aqueous buffer. The iRGD peptide was incorporated into the polymersome structure to make hypoxia-responsive iRGD-conjugated polymersomes (iPs). Doxorubicin (DOX) was encapsulated in the polymersomes to prepare both targeted and non-targeted hypoxia-responsive polymersomes (DOX-iPs and DOX-Ps, respectively). The polymeric nanoparticles released less than 30% of their encapsulated DOX within 12 hours under normoxic conditions (21% oxygen), whereas under hypoxia (2% Oxygen), doxorubicin release remarkably increased to over 95%. The targeted polymersomes significantly decreased TNBC cells' viability in monolayer and spheroid cultures under hypoxia compared to normoxia. Animal studies displayed that targeted polymersomes significantly diminished tumor growth in xenograft nude mice. Overall, the targeted polymersomes exhibited potent anti-tumor activity in monolayer, spheroid, and animal models of TNBC. With further developments, the targeted nanocarriers discussed here might have the translational potential as drug carriers for the treatment of TNBC.
Insights
Targeted hypoxia-responsive polymersomes loaded with doxorubicin (DOX) effectively treat triple-negative breast cancer (TNBC). These nanocarriers release DOX in low-oxygen tumor environments, significantly reducing cancer cell viability and tumor growth in preclinical models.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Oncology
Background:
- Triple-negative breast cancer (TNBC) is characterized by high recurrence and metastasis, often linked to low oxygen levels (hypoxia) that promote therapeutic resistance.
- Neuropilin-1 (NRP-1) receptors are overexpressed on TNBC cells, presenting a target for drug delivery.
- The iRGD peptide can bind to NRP-1, facilitating drug penetration into tumors.
Purpose of the Study:
- To develop hypoxia-responsive, targeted nanocarriers for enhanced triple-negative breast cancer (TNBC) treatment.
- To evaluate the drug release kinetics and anti-cancer efficacy of these nanocarriers in vitro and in vivo.
Main Methods:
- Synthesized hypoxia-responsive diblock PLA-diazobenzene-PEG copolymers to form polymersomes (Ps).
- Incorporated iRGD peptide into polymersomes (iPs) for NRP-1 targeting.
- Encapsulated doxorubicin (DOX) into targeted (DOX-iPs) and non-targeted (DOX-Ps) polymersomes.
- Assessed DOX release under normoxic and hypoxic conditions.
- Evaluated cytotoxicity and anti-tumor efficacy in TNBC cell lines, spheroid models, and xenograft nude mice.
Main Results:
- Polymersomes demonstrated significantly higher DOX release (>95%) under hypoxia (2% O2) compared to normoxia (<30% within 12 hours).
- Targeted DOX-iPs significantly reduced TNBC cell viability in monolayer and spheroid cultures under hypoxia.
- Animal studies showed that DOX-iPs markedly inhibited tumor growth in xenograft nude mice.
Conclusions:
- Hypoxia-responsive, iRGD-targeted polymersomes effectively deliver doxorubicin to TNBC.
- These targeted nanocarriers exhibit potent anti-tumor activity in various TNBC models.
- The developed nanocarriers show translational potential for TNBC drug delivery systems.
