<p>Tumor-targeting photodynamic therapy based on folate-modified polydopamine nanoparticles</p>

Abstract

BackgroundPhotodynamic therapy (PDT), a clinical anticancer therapeutic modality, has a long history in clinical cancer treatments since the 1970s. However, PDT has not been widely used largely because of metabolic problems and off-target phototoxicities of the current clinical photosensitizers.PurposeThe objective of the study is to develop a high-efficiency and high-specificity carrier to precisely deliver photosensitizers to tumor sites, aiming at addressing metabolic problems, as well as the systemic damages current clinical photosensitizers are known to cause.MethodsWe synthesized a polydopamine (PDA)-based carrier with the modification of folic acid (FA), which is to target the overexpressed folate receptors on tumor surfaces. We used this carrier to load a cationic phthalocyanine-type photosensitizer (Pc) and generated a PDA-FA-Pc nanomedicine. We determined the antitumor effects and the specificity to tumor cell lines in vitro. In addition, we established human cancer-xenografted mice models to evaluate the tumor-targeting property and anticancer efficacies in vivo.ResultsOur PDA-FA-Pc nanomedicine demonstrated a high stability in normal physiological conditions, however, could specifically release photosensitizers in acidic conditions, eg, tumor microenvironment and lysosomes in cancer cells. Additionally, PDA-FA-Pc nanomedicine demonstrated a much higher cellular uptake and phototoxicity in cancer cell lines than in healthy cell lines. Moreover, the in vivo imaging data indicated excellent tumor-targeting properties of PDA-FA-Pc nanomedicine in human cancer-xenografted mice. Lastly, PDA-FA-Pc nanomedicine was found to significantly suppress tumor growth within two human cancer-xenografted mice models.ConclusionOur current study not only demonstrates PDA-FA-Pc nanomedicine as a highly potent and specific anticancer agent, but also suggests a strategy to address the metabolic and specificity problems of clinical photosensitizers.

Current Advances in Photoactive Agents for Cancer Imaging and Therapy

“…Cancer cells overexpress glucose transporter 1 (GLUT-1), which can be manipulated to increase the uptake of conjugated PSs (127,128). Similar results have been seen with folate, hyaluronic acid, and transferrin (129,130).…”

Polydopamine‐Incorporated Nanoformulations for Biomedical Applications

“…Yan and co‐workers prepared a folate‐modified PDA‐based carrier and loaded it with a cationic phthalocyanine‐type photosensitizer (Pc) (PDA‐FA‐Pc) for PDT. [ 57 ] The resulting PDA‐FA‐Pc exhibited high stability, selectivity, and a low pH‐triggered drug release behavior, resulting in high phototoxicity to cancer cells. Wang et al.…”

Nanoparticles as Tools to Target Redox Homeostasis in Cancer Cells

“…Cancer-specific targeting of NPs may be obtained, taking advantage of the enhanced glycolytic rate and extracellular acidification that are characteristic of most tumors. Selective targeting of the neoplastic cells can also be achieved by conjugating NPs to metabolites (e.g., folic acid, thiamine), small peptides (e.g., integrin-binding motifs), antibodies, polysaccharides, fatty acids and nucleic acids that either recognize cancer-specific surface molecules or are preferentially taken up by cancer cells [40]. Van Driel and colleagues developed EGF-conjugated NPs containing IRDye700DX as a PS [41].…”