Hypoxia, and hypoxia inducible factor-1 (HIF-1), can induce tumor resistance to radiation therapy. To overcome hypoxia-induced radiation resistance, recent studies have described nanosystems to improve tumor oxygenation for immobilizing DNA damage and simultaneously initiate oxygen-dependent HIF-1α degradation. However, HIF-1α degradation is incomplete during tumor oxygenation treatment alone. Therefore, tumor oxygenation combined with residual HIF-1 functional inhibition is crucial to optimizing therapeutic outcomes of radiotherapy. Here, a reactive oxygen species (ROS) responsive nanoplatform is reported to successfully add up tumor oxygenation and HIF-1 functional inhibition. This ROS responsive nanoplatform, based on manganese dioxide (MnO) nanoparticles, delivers the HIF-1 inhibitor acriflavine and other hydrophilic cationic drugs to tumor tissues. After reacting with overexpressed hydrogen peroxide (HO) within tumor tissues, Mn and oxygen molecules are released for magnetic resonance imaging and tumor oxygenation, respectively. Cooperating with the HIF-1 functional inhibition, the expression of tumor invasion-related signaling molecules (VEGF, MMP-9) is obviously decreased to reduce the risk of metastasis. Furthermore, the nanoplatform could relieve T-cell exhaustion via downregulation of PD-L1, whose effects are similar to the checkpoint inhibitor PD-L1 antibody, and subsequently activates tumor-specific immune responses against abscopal tumors. These therapeutic benefits including increased X-ray-induced damage, downregulated resistance, and T-cell exhaustion related proteins expression achieved synergistically the optimal inhibition of tumor growth. Overall, this designed ROS responsive nanoplatform is of great potential in the sensitization of radiation for combating primary and metastatic tumors.

Clinically, cartilage damage is frequently accompanied with subchondral bone injuries caused by disease or trauma. However, the construction of biomimetic scaffolds to support both cartilage and subchondral bone regeneration remains a great challenge. Herein, a novel strategy is adopted to realize the simultaneous repair of osteochondral defects by employing a self‐assembling peptide hydrogel (SAPH) FEFEFKFK (F, phenylalanine; E, glutamic acid; K, lysine) to coat onto 3D‐printed polycaprolactone (PCL) scaffolds. Results show that the SAPH‐coated PCL scaffolds exhibit highly improved hydrophilicity and biomimetic extracellular matrix (ECM) structures compared to PCL scaffolds. In vitro experiments demonstrate that the SAPH‐coated PCL scaffolds promote the proliferation and osteogenic differentiation of rabbit bone mesenchymal stem cells (rBMSCs) and maintain the chondrocyte phenotypes. Furthermore, 3% SAPH‐coated PCL scaffolds significantly induce simultaneous regeneration of cartilage and subchondral bone after 8‐ and 12‐week implantation in vivo, respectively. Mechanistically, by virtue of the enhanced deposition of ECM in SAPH‐coated PCL scaffolds, SAPH with increased stiffness facilitates and remodels the microenvironment around osteochondral defects, which may favor simultaneous dual tissue regeneration. These findings indicate that the 3% SAPH provides efficient and reliable modification on PCL scaffolds and SAPH‐coated PCL scaffolds appear to be a promising biomaterial for osteochondral defect repair.

To date, no extensive literature review exists regarding potential uses of mung bean proteins and peptides. As mung bean has long been widely used as a food source, early studies evaluated mung bean nutritional value against the Food and Agriculture Organization of the United Nations (FAO)/the World Health Organization (WHO) amino acids dietary recommendations. The comparison demonstrated mung bean to be a good protein source, except for deficiencies in sulphur-containing amino acids, methionine and cysteine. Methionine and cysteine residues have been introduced into the 8S globulin through protein engineering technology. Subsequently, purified mung bean proteins and peptides have facilitated the study of their structural and functional properties. Two main types of extraction methods have been reported for isolation of proteins and peptides from mung bean flours, permitting sequencing of major proteins present in mung bean, including albumins and globulins (notably 8S globulin). However, the sequence for albumin deposited in the UniProt database differs from other sequences reported in the literature. Meanwhile, a limited number of reports have revealed other useful bioactivities for proteins and hydrolysed peptides, including angiotensin-converting enzyme inhibitory activity, anti-fungal activity and trypsin inhibitory activity. Consequently, several mung bean hydrolysed peptides have served as effective food additives to prevent proteolysis during storage. Ultimately, further research will reveal other nutritional, functional and bioactive properties of mung bean for uses in diverse applications.

Drug delivery systems are generally believed to comprise drugs and excipients. A peptide-drug conjugate is a single molecule that can simultaneously play multiple roles in a drug delivery system, such as in vivo drug distribution, targeted release, and bioactivity functions. This molecule can be regarded as an integrated drug delivery system, so it is called a molecular drug delivery system. In the context of cancer therapy, a peptide-drug conjugate comprises a tumor-targeting peptide, a payload, and a linker. Tumor-targeting peptides specifically identify membrane receptors on tumor cells, improve drug-targeted therapeutic effects, and reduce toxic and side effects. Payloads with bioactive functions connect to tumor-targeting peptides through linkers. In this review, we explored ongoing clinical work on peptide-drug conjugates targeting various receptors. We discuss the binding mechanisms of tumor-targeting peptides and related receptors, as well as the limiting factors for peptide-drug conjugate-based molecular drug delivery systems. Towards enhanced targeting on tumorsDespite the rapid development of anticancer drugs in the past few decades, cancer is one of the leading causes of death in the world [1]. Due to the lack of an effective means to distinguish tumor cells from normal cells [2], the accumulation efficiency of anticancer drugs in tumor cells is low and the toxic side effects on normal tissues are high. In the treatment process, drug resistance problems are caused by tumor heterogeneity [3], drug inactivation, transport, and metabolism, changes in drug targets, and tumor microenvironment dysfunction [4]. Although advanced drug delivery methods can partially solve problems of targeting, toxicity, and drug resistance [5], difficult industrialization, complicated process control, and huge costs remain insurmountable obstacles.Peptide-drug conjugates are emerging molecular drug delivery system (see Glossary) that achieve precise drug delivery and tumor-targeted release at the molecular level [6]. Current drug delivery systems, such as nano-drug delivery systems, use various complex excipients to assemble nanoscale particles that encapsulate drugs to be passively or actively delivered to target organs. The anticancer efficacy of nano-drug delivery systems is improved by an enhanced permeability retention effect to increase drug accumulation in tumors and the toxicity of nanodrug delivery systems is reduced by the long systemic circulation to decrease drug accumulation in normal organs [7]. However, a reappraisal of nano-drug delivery system design is suggested to improve their clinical efficacy and safety in cancer patients [8].By contrast, molecular drug delivery systems use a single peptide-drug conjugate molecule to achieve in vivo drug delivery, targeted drug release, and bioactivity, which can maximize the targeting effect and reduce drug resistance. Peptide-drug conjugates, which were first reported in 1972 by Freer et al.[9] (Box 1), are similar to the tethering of ligand-targeted drugs [10],

Tumor microenvironment with hypoxia and excess hydrogen peroxide (HO) tremendously limits the effect of chemoradiation therapy of colorectal cancer. For the first time, we developed a facile method to deposit manganese dioxide (MnO) on the surface of albumin bound paclitaxel nanoparticles (ANPs-PTX) to obtain MnO-functioned ANPs-PTX (MANPs-PTX). In the tumor microenvironment, MANPs-PTX could consume excess hydrogen peroxide (HO) to produce abundant oxygen for tumor oxygenation and improve chemoradiation therapy. Meanwhile, the released Mn from MANPs-PTX had excellent T magnetic resonance imaging (MRI) performances for tumor detection. Notably, the obtained MANPs-PTX would be a promising theranostic agent and have potential clinical application prospects.

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