Nanomedicine-based strategies to counter chemoresistance in diffuse large B-cell lymphoma

Chemoresistance is attributed to the incidence of relapse and treatment failure, despite the new advancements in chemoimmunotherapy for diffuse large B-cell lymphoma (DLBCL). The genesis of resistance is dependent on the complex interrelatedness of tumor-intrinsic factors comprising genetic and epigenetic changes, disrupted survival signaling, metabolic reprogramming, and extrinsic factors stemming from the tumor microenvironment (TME). Conventional approaches have been inadequate to address these multifactorial mechanisms, highlighting the requirement for innovative strategies. Nanomedicine approaches circumvent chemoresistance by delivering targeted chemotherapeutic compounds, molecular inhibitors, nucleic acid-based therapies, with modified TME to stimulate immune responses. Multifunctional nanocarriers co-administer multiple drug formulations and bypass efflux transporters. Additionally, they can enhance intracellular retention, restore the ability to undergo apoptosis, and improve overall therapeutic performance upon cell fusion. It thereby facilitates the on-demand release of therapeutic compounds. Preclinical studies validate the suppression of tumor growth, enhanced chemosensitivity and lessened systemic toxicity. Early clinical evidence suggests the initial feasibility of implementing nanomedicine-based strategies. The future perspectives include molecular profiling to personalize nanomedicine, AI-based optimization of nanocarrier design, and augmentation of immunotherapy and targeted agents. These strategies aim to address adaptive resistance and disease heterogeneity and achieve a substantial reduction in chemoresistant DLBCL. This review elucidates the molecular insights into the detailed mechanisms of chemoresistance in DLBCL and the developments in nanomedicine as a potential model for precision lymphoma therapy.