Nanoformulation Strategies to Overcome Multi-Drug Resistance in Cancer: A Call for Pharmacological and Translational Rigor
核心洞察
Multi-drug resistance (搜索) (MDR) remains the most formidable pharmacological barrier to effective cancer chemotherapy, causing treatment failure in the majority of patients with advanced or recurrent disease.
Advanced nanoformulations can evade efflux pump recognition, enable co-delivery of chemosensitizers with primary agents, and exploit receptor-mediated endocytosis to bypass transporter-dependent efflux.
A new Frontiers Research Topic seeks to consolidate evidence linking nanocarrier physicochemical properties to MDR circumvention, leveraging AI-guided design and cancer stem cell-targeted nanomedicines.
Multi-drug resistance (搜索) (MDR) remains the most formidable pharmacological barrier to effective cancer chemotherapy, accounting for treatment failure in the majority of patients with advanced or recurrent disease. MDR arises through diverse mechanisms that collectively reduce intracellular drug concentrations below therapeutic thresholds, and conventional chemotherapeutic regimens frequently fail to account for the dynamic, spatially heterogeneous nature of MDR within the tumor microenvironment.
Advanced nanoformulations offer a mechanistically grounded strategy to circumvent these resistance pathways. By encapsulating cytotoxic payloads within engineered nanocarriers, these systems can evade efflux pump recognition, enable spatiotemporally controlled co-delivery of chemosensitizers alongside primary agents, and exploit receptor-mediated endocytosis to bypass transporter-dependent efflux.
The Need for a Translational Framework
Despite promising nanoformulation strategies reported in isolated studies, the field lacks a coherent body of evidence that maps the relationship between nanocarrier physicochemical properties and MDR circumvention mechanisms, utilizes computational models or artificial intelligence (AI) to accelerate formulation optimization, and designs advanced nanomedicines specifically targeting cancer stem cells (CSCs).
A rigorous pharmacological and translational framework is urgently needed to systematically evaluate these approaches from formulation design through to preclinical proof-of-concept. There remains a critical need to characterize the pharmacokinetics, biodistribution, and theranostic potential of candidate systems in resistant tumor models, benchmarking formulations against regulatory-relevant preclinical endpoints required for investigational new drug (IND) filing.
Scope and Priority Themes
The Research Topic aims to address these gaps by bringing together research that elucidates the mechanistic basis by which nanoformulations overcome specific resistance pathways, leverages computational and intelligent design approaches to optimize formulation development, defines pharmacokinetic and biodistribution determinants in MDR and cancer stem cell models, and advances GMP-compatible formulation strategies, nanotheranostics, and preclinical safety profiling that support clinical translation and regulatory science.
Priority themes include AI-guided nanoformulation design, modeling, and optimization; tumor microenvironment-responsive and stimuli-triggered nanocarriers targeting MDR niches; cancer stem cell-targeted nanomedicines to circumvent therapy resistance and recurrence; and nanotheranostics integrating real-time diagnostic imaging with MDR-reversal therapeutics. Additional focus areas encompass nanocarrier-mediated efflux pump inhibition or evasion (e.g., P-gp, BCRP (搜索), MRP (搜索)), co-delivery systems for chemosensitizer–drug combinations, ADMET characterization and pharmacokinetic/pharmacodynamic (PK/PD) modeling in drug-resistant cancer models, clinical translation and regulatory science, and GMP-compatible formulation development.
Submission Requirements
Studies must demonstrate selectivity toward cancer cells across multiple cell lines and provide detailed characterization of formulation composition and stability. The Research Topic welcomes original research articles, reviews, mini-reviews, perspectives, and methods papers focused on nanoformulation-based strategies to overcome MDR in cancer, with an explicit pharmacological and/or translational dimension.
Manuscripts focused solely on natural product extracts, cancer prognosis, or therapy-related side effects are outside the scope of this section. By integrating pharmacological depth with translational rigor, the initiative aims to accelerate the development of clinically viable nanomedicines for drug-resistant cancers.