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Smart Targeting To Improve Cancer Therapeutics
Moraima Morales-Cruz1, Yamixa Delgado2, Betzaida Castillo3
1Department of Chemistry, University of Puerto Rico, Río Piedras Campus, San Juan, PR, USA.
Abstract:
Cancer is the second largest cause of death worldwide with the number of new cancer cases predicted to grow significantly in the next decades. Biotechnology and medicine can and should work hand-in-hand to improve cancer diagnosis and treatment efficacy. However, success has been frequently limited, in particular when treating late-stage solid tumors. There still is the need to develop smart and synergistic therapeutic approaches to achieve the synthesis of strong and effective drugs and delivery systems. Much interest has been paid to the development of smart drug delivery systems (drug-loaded particles) that utilize passive targeting, active targeting, and/or stimulus responsiveness strategies. This review will summarize some main ideas about the effect of each strategy and how the combination of some or all of them has shown to be effective. After a brief introduction of current cancer therapies and their limitations, we describe the biological barriers that nanoparticles need to overcome, followed by presenting different types of drug delivery systems to improve drug accumulation in tumors. Then, we describe cancer cell membrane targets that increase cellular drug uptake through active targeting mechanisms. Stimulus-responsive targeting is also discussed by looking at the intra- and extracellular conditions for specific drug release. We include a significant amount of information summarized in tables and figures on nanoparticle-based therapeutics, PEGylated drugs, different ligands for the design of active-targeted systems, and targeting of different organs. We also discuss some still prevailing fundamental limitations of these approaches, eg, by occlusion of targeting ligands.
Insights
Developing smart drug delivery systems is crucial for improving cancer treatment efficacy, especially for solid tumors. Combining passive, active, and stimulus-responsive targeting strategies enhances drug accumulation and therapeutic outcomes.
Area of Science:
- Biotechnology and Medicine
- Nanotechnology in Oncology
Background:
- Cancer remains a leading global cause of death, with increasing incidence projected.
- Current cancer therapies, particularly for late-stage solid tumors, face significant limitations.
- There is a critical need for advanced, synergistic therapeutic strategies combining effective drugs and delivery systems.
Purpose of the Study:
- To review the impact of passive targeting, active targeting, and stimulus-responsive strategies in drug delivery systems for cancer.
- To explore how combining these targeting strategies can enhance therapeutic efficacy.
- To discuss biological barriers and targeting mechanisms for nanoparticles in cancer treatment.
Main Methods:
- Review of current cancer therapies and their limitations.
- Description of biological barriers encountered by nanoparticles.
- Analysis of various drug delivery systems, including nanoparticle-based therapeutics, PEGylated drugs, and active targeting ligands.
- Discussion of stimulus-responsive drug release mechanisms.
Main Results:
- Smart drug delivery systems utilizing passive, active, and/or stimulus-responsive strategies show promise for improving drug accumulation in tumors.
- Active targeting mechanisms leverage cancer cell membrane targets to enhance cellular drug uptake.
- Stimulus-responsive systems enable drug release based on specific intra- and extracellular conditions.
Conclusions:
- Combining multiple targeting strategies (passive, active, stimulus-responsive) is effective in enhancing cancer therapy.
- Nanoparticle-based drug delivery systems offer potential for improved cancer treatment efficacy.
- Overcoming limitations such as ligand occlusion remains a key challenge for these advanced therapeutic approaches.
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