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Targeted Cancer Therapies

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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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Site-targeted drug delivery systems enhance therapeutic efficacy while minimizing systemic toxicity and treatment costs. Unlike conventional methods, these systems ensure precise drug delivery, improving bioavailability and reducing side effects. Targeted drug delivery is classified into three levels. First-order targeting directs drugs to the capillary beds of specific organs or tissues. Second-order targets specific cell types, such as tumor cells, using receptor-mediated interactions.
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Polymalic Acid-based Nano Biopolymers for Targeting of Multiple Tumor Markers: An Opportunity for Personalized Medicine?
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Programmed Nanococktail Based on pH-Responsive Function Switch for Self-Synergistic Tumor-Targeting Therapy.

Yang Li, Liang Song, Jinyan Lin

  • 1Children's Hospital of Soochow University , Suzhou 215025, Peopel's Republic of China.

ACS Applied Materials & Interfaces
|October 18, 2017
PubMed
Summary

This study developed a novel nanococktail for targeted cancer therapy, combining two drugs (epirubicin and methotrexate) into one nanoparticle. This system enhances drug delivery and anticancer efficacy by targeting folate receptors and responding to acidic tumor environments.

Keywords:
combination cancer therapyepirubicinpH-responsiveself-assemblytargeting methotrexate prodrug

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Area of Science:

  • Biomedical Engineering
  • Nanotechnology
  • Oncology

Background:

  • Combination chemotherapy improves therapeutic index but faces challenges in nanoparticle (NP) surface functionalization.
  • Achieving multiple functions from a single ligand on NP surfaces remains a significant hurdle.
  • Methotrexate (MTX), an anticancer drug with folate-like targeting, can be modified for dual-functionality.

Purpose of the Study:

  • To synthesize an acid-induced, "targeting-anticancer" switching nanoparticle system for combination chemotherapy.
  • To create a nanococktail for co-delivery of epirubicin (EPI) and MTX, enhancing tumor targeting and drug release.
  • To investigate the synergistic anticancer efficiency and in vivo performance of the developed nanosystem.

Main Methods:

  • Synthesized DSPE-PEG-CH═N-MTX using a pH-sensitive imine bond for MTX conjugation.
  • Co-self-assembled epirubicin-phospholipid (PC) complex and DSPE-PEG-CH═N-MTX to form MTX-PEG-EPI-PC NPs.
  • Evaluated NP targeting of folate receptors, acid-triggered drug release, intracellular drug delivery, and in vivo anticancer efficacy.

Main Results:

  • The MTX-PEG-EPI-PC NPs successfully targeted folate receptor-overexpressing tumor cells.
  • Acidic endo/lysosomes triggered on-demand release of EPI and MTX, demonstrating synergistic anticancer effects.
  • In vivo studies showed significantly enhanced tumor accumulation and efficacy for NPs with cleavable imine bonds compared to controls.

Conclusions:

  • The developed nanococktail offers a promising strategy for self-synergistic tumor-targeting therapy.
  • Acid-cleavable functionalization enables combined active targeting and on-demand drug release.
  • This approach enhances anticancer efficacy and may improve the therapeutic index in cancer treatment.