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The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
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Polymalic Acid-based Nano Biopolymers for Targeting of Multiple Tumor Markers: An Opportunity for Personalized Medicine?
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Precise Ratiometric Drug Delivery for the Treatment of Triple-Negative Breast Cancer.

Rae Hyung Kang1,2, Morteza Rasoulianboroujeni1,3, Maryam Kianpour1

  • 1Pharmaceutical Sciences Division, School of Pharmacy, University of Wisconsin-Madison, Madison, Wisconsin 53705, United States.

ACS Nano
|November 19, 2025
PubMed
Summary

Rapaxane, a novel nanotechnology formulation, effectively treats triple-negative breast cancer (TNBC) by combining paclitaxel and rapamycin. This advanced drug delivery system enhances efficacy and reduces toxicity in preclinical TNBC models.

Keywords:
paclitaxelpolymeric micellerapamycinratiometric drug deliverytriple-negative breast cancer

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Area of Science:

  • Biomedical Engineering
  • Nanotechnology
  • Oncology

Background:

  • Triple-negative breast cancer (TNBC) presents significant treatment challenges due to its aggressive nature and lack of targeted therapies.
  • Current combination therapies with paclitaxel (PTX) and rapamycin (RAP) face limitations in pharmacokinetics and toxicity.
  • Nanotechnology offers potential solutions for improved drug delivery and therapeutic outcomes in TNBC.

Purpose of the Study:

  • To develop and evaluate Rapaxane, a polymeric micelle formulation co-delivering PTX and RAP prodrugs at a synergistic ratio for TNBC treatment.
  • To assess the in vitro and in vivo efficacy, safety, and drug release characteristics of Rapaxane compared to existing therapies.
  • To demonstrate the potential of nanotechnology-based ratiometric drug delivery systems for overcoming combination therapy limitations.

Main Methods:

  • Formulation of Rapaxane using polymeric micelles co-loaded with oligo(lactic acid)8-conjugated PTX (oLA8-PTX) and RAP (oLA8-RAP) prodrugs at a 5:1 ratio.
  • In vitro cytotoxicity assays using TNBC cell lines (4T1, MDA-MB-231).
  • Characterization of encapsulation, stability, and drug release using DLS and RP-HPLC.
  • In vivo efficacy studies in subcutaneous and orthotopic TNBC mouse models, including tumor growth, metastasis assessment (H&E, Ki-67 staining), and survival analysis.
  • Hemolysis assays to evaluate intravenous administration safety.

Main Results:

  • Rapaxane exhibited significant in vitro cytotoxicity against TNBC cell lines.
  • Confirmed ratiometric encapsulation, stability, synchronized release, and conversion of oLA8-PTX and oLA8-RAP.
  • Hemolysis assays showed negligible toxicity, indicating safety for intravenous use.
  • In vivo studies demonstrated Rapaxane's significant reduction in tumor growth and metastasis, alongside improved survival rates in TNBC models.
  • Histological analyses confirmed Rapaxane's efficacy in inhibiting lung metastasis.

Conclusions:

  • Rapaxane, a nanotechnology-based ratiometric drug delivery system, effectively enhances therapeutic efficacy for TNBC.
  • The formulation overcomes pharmacokinetic disparities and toxicity concerns associated with conventional PTX and RAP combinations.
  • Rapaxane shows significant potential as a next-generation therapy for aggressive cancers like TNBC, highlighting the promise of advanced drug delivery systems.