Cell targeting peptide guided nanomedicine: a new paradigm in precision oncology for the management of non-small cell lung cancer.

Abstract

Non-Small Cell Lung Cancer (NSCLC) remains a leading cause of cancer-related mortality worldwide owing to its high prevalence, metastatic potential, therapeutic resistance and poor survival outcomes. Effective management of NSCLC is hindered by the heterogeneous tumor microenvironment (TME), non-selective drug biodistribution, systemic toxicity, limited tumor accumulation and rapid drug clearance. Nanocarriers (NCs) represent a promising approach for cancer therapy by improving drug solubility, stability, and pharmacokinetics. However, their clinical performance is often compromised by inadequate tumor selectivity, immune-mediated clearance and restricted cellular internalization. In this context, Cell Targeting Peptides (CTPs) have gained considerable attention as versatile ligands owing to their tumor homing capability, receptor-specific recognition, superior tissue penetration, and facile surface functionalisation. The integration of CTPs with NCs represents a progressive strategy to enhance targeted delivery and therapeutic efficacy in NSCLC. The current review elucidates the pathophysiological complexity of NSCLC and prominent overexpressed receptors that can be harnessed for peptide-mediated targeting. It further discusses peptide discovery, optimization, and conjugation methodologies while critically evaluating the applications of CTP-functionalized NCs in chemotherapy, immunotherapy, phototherapy, gene delivery and tumor imaging. Moreover, the review delineates translational, manufacturing and regulatory hurdles, together with prospective approaches for advancing CTP-engineered nanotherapeutics toward clinical application in NSCLC.