Nanomedicine-Integrated Phototherapy for Cancer Theranostics: A Systematic Review of Photoresponsive Materials, Mechanisms, and Clinical Translation.

BACKGROUND

Cancer remains a principal cause of mortality worldwide, and conventional treatments are constrained by non-specific cytotoxicity, therapeutic resistance, and incomplete tumor eradication. Nanomedicine-integrated phototherapy, encompassing photodynamic therapy (PDT) and photothermal therapy (PTT), has emerged as a spatiotemporally controlled theranostic modality with demonstrated preclinical promise.

OBJECTIVE

This systematic review synthesizes current evidence on nanomedicine-based phototherapeutic agents across four research dimensions: nanotechnology design, phototherapeutic mechanisms, photoresponsive materials, and clinical translation.

METHODS

A systematic literature search was conducted across PubMed, Scopus, Web of Science, and Embase (2000-2024) using predefined search terms related to nanomedicine, PDT, PTT, and cancer theranostics. Studies were screened according to PRISMA-aligned inclusion and exclusion criteria. A total of 1847 records were identified; following deduplication and full-text review, 78 studies met eligibility criteria and were included in the narrative synthesis.

RESULTS

Nanocarrier design has advanced substantially, with enhanced permeability and retention (EPR)-mediated and active-targeted platforms achieving 10-50-fold tumor-to-tissue concentration ratios in preclinical models. Photoresponsive nanomaterials (including gold nanostructures with PCE 50-99%, carbon-based nanomaterials with PCE 40-80%, and hybrid metal-organic frameworks) demonstrate tunable optical properties suitable for NIR-activated therapy. Multifunctional theranostic platforms combining PDT or PTT with chemotherapy, immunotherapy, and multimodal imaging show synergistic efficacy. Clinical translation remains limited, with gold nanoshells (AuroLase Therapy, Nanospectra Biosciences) in Phase I evaluation for prostate cancer and several PDT photosensitizer formulations carrying regulatory approval.

CONCLUSION

Nanomedicine-integrated phototherapy addresses fundamental limitations of conventional oncology. Realizing its clinical potential requires development of biodegradable nanocarriers, standardized characterization protocols, companion diagnostics for patient stratification, and coordinated regulatory pathways. EPR variability in human tumors and the predominance of preclinical data necessitate a calibrated assessment of translational feasibility.