Endosomal escape: a bottleneck in intracellular delivery

Area of Science:

• Biotechnology
• Pharmacology
• Cell Biology

Background:

• Advances in therapeutic science introduce novel bioactive molecules like oligonucleotides, proteins, and antibodies.
• These molecules target intracellular components but face bioavailability issues due to endosomal entrapment.
• The endosomal pathway acts as a significant barrier, leading to degradation and treatment failure.

Purpose of the Study:

• To review strategies for overcoming the endosomal barrier for enhanced intracellular delivery of bioactive molecules.
• To explore mechanisms employed by microbes and novel polymeric systems for endosomal escape.
• To improve the cytosolic bioavailability of therapeutic agents.

Main Methods:

• Review of existing literature on microbial and synthetic strategies for endosomal escape.
• Analysis of mechanisms such as membrane fusion, pore formation, and proton sponge effects.
• Examination of smart polymeric carriers responsive to intracellular stimuli (pH, enzymes, temperature) and physical disruption methods.

Main Results:

• Microbial strategies offer insights into efficient host cell membrane penetration.
• Smart polymeric carriers demonstrate potential for triggered endosomal escape.
• Various methods like membrane fusion, pore formation, and stimuli-responsive systems facilitate cytosolic delivery.

Conclusions:

• Effective endosomal escape is crucial for the therapeutic efficacy of intracellularly delivered bioactives.
• Harnessing microbial mechanisms and designing smart carriers are promising avenues for improving drug delivery.
• Further research into these strategies can overcome bioavailability limitations and enhance treatment outcomes.