Ligand-Targeted Delivery of Photosensitizers for Cancer Treatment

Abstract

Photodynamic therapy (PDT) is a promising cancer treatment which involves a photosensitizer (PS), light at a specific wavelength for PS activation and oxygen, which combine to elicit cell death. While the illumination required to activate a PS imparts a certain amount of selectivity to PDT treatments, poor tumor accumulation and cell internalization are still inherent properties of most intravenously administered PSs. As a result, common consequences of PDT include skin photosensitivity. To overcome the mentioned issues, PSs may be tailored to specifically target overexpressed biomarkers of tumors. This active targeting can be achieved by direct conjugation of the PS to a ligand with enhanced affinity for a target overexpressed on cancer cells and/or other cells of the tumor microenvironment. Alternatively, PSs may be incorporated into ligand-targeted nanocarriers, which may also encompass multi-functionalities, including diagnosis and therapy. In this review, we highlight the major advances in active targeting of PSs, either by means of ligand-derived bioconjugates or by exploiting ligand-targeting nanocarriers.

Nanoparticle-Mediated Delivery Systems in Photodynamic Therapy of Colorectal Cancer

“…One of the desirable properties of the targeting moieties that are conjugated onto the NP is their high affinity as well as their capability to specifically recognize and actively bind to the appropriate antigens or receptors that are exclusively or uniquely overexpressed on only the targeted CRC cells [5]. Subsequently, NP-PS internalisation through receptor-mediated endocytosis is improved and PS delivery is enhanced [94]. Table 3 summarizes the studies that investigated active PS delivery in CRC.…”

Targeted Photodynamic Diagnosis and Therapy for Esophageal Cancer: Potential Role of Functionalized Nanomedicine

“…These above NPs platforms can be functionalized using unique tumor targeting surface receptors or ligand agents such as monoclonal antibodies (mAb), antibody fragments, aptamers and nucleic acid, small molecules, and peptides. These ligands are added to the surface of NPs, enabling the optimal coupling of the nanocarrier PS conjugates to overexpress cancer surface recognition molecules, such as epidermal growth factor receptors (EGFR), folate receptors (FR), transferrin receptors (TfR), CD44, and CD133, to improve PS subcellular internalization and accumulation [96][97][98]. Two main strategies are employed for efficient delivery and localization of functionalized NPPS drugs to the target cancer cells: active and passive nanotargeted drug delivery systems (Table 4).…”

“…Passive targeting strategy solely relies on the physicochemical properties of PS drugs/NPs and the pathophysiological characters of the cancer cells. It is hypothesized that the EPR effect, which takes advantage of the porous tumor endothelium, and the weak tumor lymphatic drainage, promote the selective localization of the PS drugs/NPs in cancer cells (Figure 3) [81,97,98]. Active targeting refers to the cellular and molecular tumor site interactions through surface antigens (Figure 3).…”

Viral Nanoparticle System: An Effective Platform for Photodynamic Therapy

“…In this process, reactive oxygen species (ROS), which are cytotoxic to tumor cells, are efficiently produced from the photochemical reaction, mediated by photosensitizers irradiated by light, and induce cellular inflammatory responses ( Figure 1 ) [ 5 , 6 ]. This pathway involves two types of ROS [ 7 , 8 , 9 ]: Type I reactions involve electron transfer reactions that produce a series of ROS such as hydrogen peroxide, hydroxyl radicals, and superoxide anions; Type II reactions involve energy transfer, leading to singlet oxygen generation, which is considered the main mechanism [ 10 , 11 , 12 ]. In the second type, photons are absorbed by the ground state of the photosensitizer.…”