Photochemical internalization enhanced macrophage delivered chemotherapy

Abstract

Background Macrophage (Ma) vectorization of chemotherapeutic drugs has the advantage for cancer therapy in that it can actively target and maintain an elevated concentration of drugs at the tumor site, preventing their spread into healthy tissue. A potential drawback is the inability to deliver a sufficient number of drug-loaded Ma into the tumor, thus limiting the amount of active drug delivered. This study examined the ability of photochemical internalization (PCI) to enhance the efficacy of released drug by Ma transport. Methods Tumor spheroids consisting of either F98 rat glioma cells or F98 cells combined with a subpopulation of empty or doxorubicin (DOX)-loaded mouse Ma (RAW264.7) were used as in vitro tumor models. PCI was performed with the photosensitizer AlPcS2a and laser irradiation at 670 nm. Results RAW264.7 Ma pulsed with DOX released the majority of the incorporated DOX within two hours of incubation. PCI significantly increased the toxicity of DOX either as pure drug or derived from monolayers of DOX-loaded Ma. Significant growth inhibition of hybrid spheroids was also observed with PCI even at subpopulations of DOX-loaded Ma as low as 11% of the total initial hybrid spheroid cell number. Conclusion Results show that RAW264.7 Ma, pulsed with DOX, could effectively incorporate and release DOX. PCI significantly increased the ability of both free and Ma-released DOX to inhibit the growth of tumor spheroids in vitro. The growth of F98+DOX loaded Ma hybrid spheroids were synergistically reduced by PCI, compared to either photodynamic therapy or released DOX acting alone.

Biomimetic Gold Nanoshell-Loaded Macrophage for Photothermal Biomedicine

“…To overcome these limitations, cancer therapies using immune cells have recently been proposed in which immune cells function as vectors or carriers for the delivery of therapeutic agents [6,11,[16][17][18]. The biomimetic delivery system (BDS) has been emerging as a novel strategy due to its inherent tumor-homing tendency and biocompatibility [19]. The basic theory of BDS is the chemotaxis of certain cells; a variety of cytokines secreted by tumor cells attract immune cells, which accumulate in tumor sites.…”

Exosomes Derived from Nanocomplex-Loaded Macrophages for Targeted Delivery of Docetaxel and siPLK1 against Castrate-Resistance Prostate Cancer

“…Therefore, more DTX was delivered into macrophages by Co-PMs to result in the secretion of exosomes containing more DTX. On the other hand, Co-PMs encapsulate DTX within the micelles, reducing the intracellular free DTX and thereby reducing the total DTX excreted by the powerful P-gp e ux pathway of the macrophage [24,25].…”

Enhancing the effects of chemotherapy by combined macrophage-mediated photothermal therapy (PTT) and photochemical internalization (PCI)

“…Efficient drug delivery by macrophages has also recently been demonstrated both with and without PCI [41–43]. Macrophages loaded with a combination of drug and AuNS for combined PTT-PCI are now under investigation, both in vitro and in animal models.…”