Recent Advances in Tumor Microenvironment Responsive Formulations and Delivery Systems for Anticancer Therapy

Dear Colleagues,

Recent years have seen rapid progress in tumor microenvironment (TME) responsive formulations that convert hallmark TME features into actionable triggers for selective delivery and activation. Acidic extracellular pH, hypoxia, oxidative and reductive stress, enzyme rich niches, abnormal perfusion, and immunosuppressive signaling collectively impede transport and intracellular access, yet these same cues enable smart release, conditional activation, and improved therapeutic index. This Special Issue invites original research and authoritative reviews on TME responsive formulation and delivery strategies for anticancer therapy, spanning nanoparticles and beyond, including prodrugs, stimuli responsive polymers, lipid systems, hydrogels, depots, and device enabled delivery. We encourage rigorous physicochemical characterization, mechanistic insight on trigger response and intratumoral fate, and quantitative evaluation using relevant in vitro and in vivo models. Studies integrating biodistribution, imaging, and PK/PD, as well as manufacturability, stability, quality by design, and regulatory relevant CMC, are particularly welcome. By highlighting recent advances and translationally credible evidence, this Issue aims to accelerate development of safer and more effective TME-guided cancer therapeutics.

We are pleased to invite submissions to the Special Issue ‘Recent Advances in Tumor Microenvironment Responsive Formulations and Delivery Systems for Anticancer Therapy’. Many anticancer candidates underperform in vivo not because of insufficient potency, but because the tumor microenvironment creates delivery barriers that suppress intratumoral exposure and widen systemic toxicity. Hallmark TME features, including acidic extracellular pH, hypoxia, oxidative stress, redox gradients, protease activity, dense extracellular matrix, and elevated interstitial pressure, can impede penetration, cellular uptake, and subcellular access.

This Special Issue aims to curate a focused collection of original research articles and reviews that connect pharmaceutic design with tumor microenvironment biology, highlighting how TME responsive formulation and delivery choices can produce measurable improvements in tumor targeting, efficacy, and safety. The topic is fully within the scope of Pharmaceutics, as it centers on formulation science, biopharmaceutics, pharmacokinetics, controlled release, drug delivery, and translational pharmaceutics, with a clear emphasis on quantitative evaluation and practical development considerations. We concentrate on TME triggers such as pH, redox and ROS, hypoxia, and enzymes, and on formulation and delivery platforms that are experimentally and translationally grounded.

In this Special Issue, original research articles and reviews are welcome. Research areas may include (but are not limited to) the following:

• pH responsive drug release and tumor activated formulations;
• Redox- or ROS-triggered delivery systems for improved tumor selectivity;
• Enzyme responsive carriers and prodrugs for cancer therapy;
• TME-guided delivery for immunotherapy and combination therapy;
• Beyond nanoparticles: hydrogels, depots, implants, microneedles, and local or regional delivery;
• Approaches to improve tumor penetration and intratumoral distribution, including stroma and ECM focused strategies;
• How to evaluate performance: biodistribution, imaging, tumor penetration assays, and PK/PD links.

I look forward to receiving your contributions.

Dr. Hyun-Ouk Kim
Guest Editor

Manuscript Submission Information

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Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

• tumor microenvironment
• stimuli responsive formulation
• pH responsive delivery
• redox responsive delivery
• enzyme triggered release
• biodistribution