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Responsive Nanocarriers as an Emerging Platform for Cascaded Delivery of Nucleic Acids to Cancer
Yang Liu1, Cong-Fei Xu2, Shoaib Iqbal1
1School of Life Sciences, University of Science & Technology of China, Hefei, Anhui, 230027, P.R. China.
Abstract:
Cascades of systemic and intracellular obstacles, including low stability in blood, little tumor accumulation, weak tumor penetration, poor cellular uptake, inefficient endosomal escape and deficient disassembly in the cytoplasm, must be overcome in order to deliver nucleic acid drugs for cancer therapy. Nanocarriers that are sensitive to a variety of physiological stimuli, such as pH, redox status, and cell enzymes, are substantially changing the landscape of nucleic acid drug delivery by helping to overcome cascaded systemic and intracellular barriers. This review discusses nucleic acid-based therapeutics, systemic and intracellular barriers to efficient nucleic acid delivery, and nanocarriers responsive to extracellular and intracellular biological stimuli to overcome individual barriers. In particular, responsive nanocarriers for the cascaded delivery of nucleic acids in vivo are highlighted. Developing novel cascaded nanocarriers that transform their physicochemical properties in response to various stimuli in a timely and spatially controlled manner for nucleic acid drug delivery holds great potential for translating the promise of nucleic acid drugs and achieving clinically successful cancer therapy.
Insights
Responsive nanocarriers overcome barriers for nucleic acid cancer therapy. These advanced drug delivery systems are key to improving cancer treatment efficacy and clinical success.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Cancer Therapeutics
Background:
- Nucleic acid drugs face systemic and intracellular barriers, limiting cancer therapy efficacy.
- These obstacles include poor stability, tumor accumulation, penetration, cellular uptake, endosomal escape, and cytoplasmic disassembly.
- Stimuli-responsive nanocarriers offer a promising solution to overcome these cascaded challenges.
Purpose of the Study:
- To review nucleic acid-based therapeutics and their delivery barriers in cancer therapy.
- To discuss the role of stimuli-responsive nanocarriers in overcoming systemic and intracellular obstacles.
- To highlight advanced nanocarrier strategies for effective in vivo nucleic acid drug delivery.
Main Methods:
- Literature review of nucleic acid therapeutics and nanocarrier strategies.
- Analysis of systemic and intracellular barriers in cancer drug delivery.
- Discussion of nanocarriers responsive to biological stimuli (pH, redox, enzymes).
Main Results:
- Stimuli-responsive nanocarriers effectively address multiple barriers in nucleic acid drug delivery.
- Extracellular and intracellular stimuli-responsive nanocarriers facilitate targeted drug release.
- Cascaded nanocarriers demonstrate potential for overcoming sequential delivery challenges in vivo.
Conclusions:
- Responsive nanocarriers are transforming nucleic acid drug delivery for cancer therapy.
- Developing novel cascaded nanocarriers with controlled property transformation is crucial.
- These advancements hold significant potential for clinical translation and successful cancer treatment.
