Biochemical and Molecular Perspectives on Engineered Nanoparticles for Cancer Therapy

Dear Colleagues,

The advent of engineered nanoparticles (ENPs) offers a revolutionary approach to cancer treatment by leveraging molecular-level precision to enhance therapeutic efficacy and minimize systemic toxicity. This Special Issue delves into the intricate biochemical pathways and molecular mechanisms that enable the design and application of ENPs as targeted delivery systems for cancer therapy, with a particular focus on emerging therapeutic targets such as apoptosis, ferroptosis, and oxidative stress regulation.

1. Molecularly Driven Nanoparticle Design:

- Cutting-edge research highlights the development of ENPs with surface modifications tailored to interact with specific molecular markers such as HER2, estrogen receptors, and other cancer-associated proteins. These ligands exploit receptor-mediated pathways to enhance cell-specific uptake.

- Multifunctional ENPs are explored for their ability to integrate therapeutic agents, molecular imaging tools, and multimodal treatment strategies, with a focus on the molecular dynamics at the cancer cell interface.

2. Mechanistic Insights into Targeting Pathways:

- This issue investigates the molecular basis of the enhanced permeability and retention (EPR) effect in tumors, alongside active targeting mechanisms, such as receptor-mediated endocytosis and intracellular trafficking pathways. Detailed discussions include the role of nanoparticle chemistry in optimizing these processes.

- A spotlight is placed on ENPs targeting novel cell death pathways, particularly ferroptosis—a form of iron-dependent, oxidative stress-mediated cell death. This emerging mechanism provides new therapeutic opportunities to address apoptosis-resistant cancer subtypes.

3. Therapeutic Mechanisms and Molecular Interactions:

- Contributions highlight how ENPs facilitate the intracellular delivery of chemotherapy agents, gene editing technologies (e.g., CRISPR/Cas9), and RNA interference molecules, emphasizing their interactions with cellular signaling cascades, DNA repair pathways, and apoptotic or ferroptotic processes.

- The issue delves into the role of ENPs in modulating oxidative stress and lipid peroxidation as central biochemical mechanisms underlying ferroptosis induction. This oxidative vulnerability in cancer cells is explored as a promising avenue for therapy.

4. Biological and Biochemical Challenges:

- Discussions focus on the molecular interactions of ENPs with the tumor microenvironment, including the role of the extracellular matrix, immune responses, and intracellular trafficking barriers. Particular emphasis is placed on ENPs' capacity to generate or mitigate oxidative stress, their potential off-target effects, and the biochemical challenges of biocompatibility and cytotoxicity.

5. Future Directions:

- Prospective research emphasizes the integration of systems biology and bioinformatics to design ENPs tailored to individual molecular tumor profiles. Advances in real-time molecular imaging and biosensing are explored as tools to monitor therapeutic efficacy and nanoparticle behavior at the cellular level.

- The implications of oxidative stress modulation in targeting cancer cells, particularly in combination with ferroptosis-inducing ENPs, are highlighted as a promising future direction. These studies underscore the potential of ENPs to exploit cancer cell vulnerabilities tied to redox imbalances and lipid metabolism.

This Special Issue underlines the transformative potential of engineered nanoparticles in cancer therapy, particularly through the lens of their molecular and biochemical mechanisms. By unraveling the fundamental interactions between ENPs and cancer cells—ranging from targeting established pathways to exploiting ferroptosis and oxidative stress—these studies pave the way for precision medicine approaches that promise to redefine cancer management. Future efforts will require interdisciplinary collaboration to address existing challenges and accelerate the translation of these technologies into clinical applications. Pharmaceutics invites submissions related to drug delivery systems and innovative formulations, while Biomedicine encourages contributions centered on biological aspects.

You may choose our Joint Special Issue in Biomedicines.

Prof. Dr. Luca Vanella
Dr. Valeria Consoli
Guest Editors

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• cancer
• oxidative stress
• engineered nanoparticles (ENPs)
• drug delivery
• biochemical processes
• ferroptosis
• apoptosis
• cell death
• molecular interactions
• tumor microenvironment