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Colorectal cancer (CRC) is a usual digestive tract malignancy and the third main cause of cancer death around the world, with a high occurrence rate and mortality rate. Conventional therapies for CRC have certain side effects and restrictions. However, the exciting thing is that with the rapid development of nanotechnology, nanoparticles have gradually become more valuable drug delivery systems than traditional therapies because of their capacity to control drug release and target CRC. This also promotes the application of nano-drug targeted delivery systems in the therapy of CRC. Moreover, to make nanoparticles have a better colon targeting effect, many approaches have been used, including nanoparticles targeting CRC and in response to environmental signals. In this review, we focus on various targeting mechanisms of CRC-targeted nanoparticles and their latest research progress in the last three years, hoping to give researchers some inspiration on the design of CRC-targeted nanoparticles.

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Poly(ethylene glycol) (PEG) has been widely applied in biomedical field as a gold standard. The conjugation of PEG to proteins, peptides, oligonucleotides (DNA, small interfering RNA (siRNA), microRNA (miRNA)) and nanoparticles, also known as PEGylation, is a common method to improve the efficiency of drug delivery and pharmacokinetics in vivo. The effect of PEGylation on the in vivo fate of various formulations has been and continues to be extensively studied based on the successful PEGylation of proteins to improve in vivo circulation time and reduce immunogenicity. The PEG shell protects the particles from aggregation, immune recognition, and phagocytosis, thereby prolonging the in vivo circulation time. This article mainly describes the development background, advantages and applications of PEGylation in the field of drug delivery, its defects or development bottlenecks, and possible alternatives.

Photodynamic therapy (PDT) is a promising approach to cancer treatment, but the heterogeneity of the tumor microenvironment (TME) limits its application. Tumor vasculature is thought to be involved in abnormal TME. Therefore, tumor vascular normalization (TVN) is expected to be a strategy to reshape TME. We prepared a graded-release nanodrug combining TVN and PDT, named as PEVM, with the core of lipid nanoparticles for sustained release of anti-angiogenic drugs and the shell of a pH-sensitive polymer linked to a photosensitizer, and evaluated its therapeutic effect on a breast cancer model. We found that PEVM could achieve mutual benefits in both therapeutic effects. TVN not only increased the intratumoral oxygen level as a raw material for PDT, but also activated the anti-tumor immune response, further improving the efficacy of PDT. PEVM showed favorable anti-tumor efficiency and exhibited the potential of combining TVN and PDT.