Abstract
Advantages such as strong signal strength, resistance to photobleaching, tunable fluorescence emissions, high sensitivity, and biocompatibility are the driving forces for the application of fluorescent nanoparticles (FNPs) in cancer diagnosis and therapy. In addition, the large surface area and easy modification of FNPs provide a platform for the design of multifunctional nanoparticles (MFNPs) for tumor targeting, diagnosis, and treatment. In order to obtain better targeting and therapeutic effects, it is necessary to understand the properties and targeting mechanisms of FNPs, which are the foundation and play a key role in the targeting design of nanoparticles (NPs). Widely accepted and applied targeting mechanisms such as enhanced permeability and retention (EPR) effect, active targeting, and tumor microenvironment (TME) targeting are summarized here. Additionally, a freshly discovered targeting mechanism is introduced, termed cell membrane permeability targeting (CMPT), which improves the tumor-targeting rate from less than 5% of the EPR effect to more than 50%. A new design strategy is also summarized, which is promising for future clinical targeting NPs/nanomedicines design. The targeting mechanism and design strategy will inspire new insights and thoughts on targeting design and will speed up precision medicine and contribute to cancer therapy and early diagnosis.
Highlights
In 1948, it was discovered that cytotoxic folate antimetabolites could treat childhood leukemia[1] and the basic approach for cancer therapy has remained the same way: surgery followed by chemotherapy with various cytotoxic compounds or radiation.[2]
The passive targeting mainly refers to the enhanced permeability and retention (EPR) effect, which was first proposed by Matsumura and Maeda in 1986.[38,39] Maeda found that a polymer accumulated in tumor tissues when conjugated with the anticancer protein
Two types of cellular targeting are distinguished: active targeting to cancer cells due to the overexpression of transferrin, folate, epidermal growth factor (EGF), or glycoproteins and so on and active targeting to the tumor endothelium due to the overexpression of the vascular endothelial growth factors (VEGF), αvβ3 integrins, the vascular cell adhesion molecule-1 (VCAM-1) or matrix metalloproteinases (MMP) etc
Summary
In 1948, it was discovered that cytotoxic folate antimetabolites could treat childhood leukemia[1] and the basic approach for cancer therapy has remained the same way: surgery followed by chemotherapy with various cytotoxic compounds or radiation.[2]. The CMPT mechanism will stimulate new insights for the targeting design, accelerate the development of tumor precision medicine, and contribute to cancer treatment and early diagnosis
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