Current cancer nanomedicines can only mitigate adverse effects but fail to enhance therapeutic efficacies of anticancer drugs. Rational design of next-generation cancer nanomedicines should aim to enhance their therapeutic efficacies. Taking this into account, this review first analyzes the typical cancer-drug-delivery process of an intravenously administered nanomedicine and concludes that the delivery involves a five-step CAPIR cascade and that high efficiency at every step is critical to guarantee high overall therapeutic efficiency. Further analysis shows that the nanoproperties needed in each step for a nanomedicine to maximize its efficiency are different and even opposing in different steps, particularly what the authors call the PEG, surface-charge, size and stability dilemmas. To resolve those dilemmas in order to integrate all needed nanoproperties into one nanomedicine, stability, surface and size nanoproperty transitions (3S transitions for short) are proposed and the reported strategies to realize these transitions are comprehensively summarized. Examples of nanomedicines capable of the 3S transitions are discussed, as are future research directions to design high-performance cancer nanomedicines and their clinical translations.

A "cluster-bomb"-like lipid-dendrimer nanoassembly synergizes the functions of its components and thereby efficiently accomplishes the drug delivery cascade for high efficacy in treating cancer. The nanoassembly successfully circulates in the blood and accumulates in the tumor. Once in the tumor, it releases small dendrimers that act like "bomblets", enabling tumor penetration, cell internalization, and drug release.

Cell-penetrating peptides (CPPs) such as transactivator of transcription (TAT) peptide have long been explored for promoting in vitro cell penetration and nuclear targeting of various cargos, but their positive charges cause strong nonspecific interactions, making them inapplicable for many in vivo applications. In this work, we used TAT to demonstrate a molecular modification approach for inhibiting nonspecific interactions of CPPs in the bloodstream while reactivating their functions in the targeted tissues or cells. The TAT lysine residues' amines were amidized to succinyl amides ((a)TAT), completely inhibiting TAT's nonspecific interactions in the blood compartment; once in the acidic tumor interstitium or internalized into cell endo/lysosomes, the succinyl amides in the (a)TAT were quickly hydrolyzed, fully restoring TAT's functions. Thus, (a)TAT-functionalized poly(ethylene glycol)-block-poly(ε-caprolactone) micelles achieved long circulation in the blood compartment and efficiently accumulated and delivered doxorubicin to tumor tissues, giving rise to high antitumor activity and low cardiotoxicity. This amidization strategy effectively and easily enables in vivo applications of CPPs.

Chimeric antigen receptor (CAR) T-cell therapy is highly effective in the treatment of B-cell acute lymphoblastic leukemia (ALL) or B-cell lymphoma, providing alternative therapeutic options for patients who failed to respond to conventional treatment or relapse. Moreover, it can bridge other therapeutic strategies and greatly improve patient prognosis, with broad applicable prospects. Even so, 30–60% patients relapse after treatment, probably due to persistence of CAR T-cells and escape or downregulation of CD19 antigen, which is a great challenge for disease control. Therefore, understanding the mechanisms that underlie post-CAR relapse and establishing corresponding prevention and treatment strategies is important. Herein, we discuss post-CAR relapse from the aspects of CD19-positive and CD19-negative and provide some reasonable prevention and treatment strategies.

The underlying mechanisms of wound healing are complex but inflammation is one of the determining factors. Besides its traditional role in combating against infection upon injury, the characteristics and magnitude of inflammation have dramatic impacts on the pathogenesis of scar. Keloids and hypertrophic scars are pathological scars that result from aberrant wound healing. They are characterized by continuous local inflammation and excessive collagen deposition. In this review, we aim at discussing how dysregulated inflammation contributes to the pathogenesis of scar formation. Immune cells, soluble inflammatory mediators, and the related intracellular signal transduction pathways are our three subtopics encompassing the events occurring in inflammation associated with scar formation. In the end, we enumerate the current and potential medicines and therapeutics for suppressing inflammation and limiting progression to scar. Understanding the initiation, progression, and resolution of inflammation will provide insights into the mechanisms of scar formation and is useful for developing effective treatments.

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Chimeric antigen receptor (CAR) T-cell therapy has yielded impressive outcomes and transformed treatment algorithms for hematological malignancies. To date, five CAR T-cell products have been approved by the US Food and Drug Administration (FDA). Nevertheless, some significant toxicities pose great challenges to the development of CAR T-cell therapy, most notably cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Understanding the mechanisms underlying these toxicities and establishing prevention and treatment strategies are important. In this review, we summarize the mechanisms underlying CRS and ICANS and provide potential treatment and prevention strategies.

Aliphatic polyester dendrimers are attractive carriers for in vivo delivery of bioactive molecules due to their biocompatibility and biodegradability, but efficient precision synthesis of these dendrimers without tedious purifications remains challenging. Herein, we report an efficient synthesis approach to polyester dendrimers from two AB2-type monomers via combining a click reaction of thiol/acrylate Michael addition with esterification. The reaction solution of each generation contains only the targeted dendrimer macromolecules; thus, the only required separation is simple precipitation. The resulting hydroxyl-terminated fifth-generation dendrimer is thermoresponsive with a LCST of 41 °C. The dendrimer could be further pegylated to obtain a water-soluble biocompatible dendrimer capable of encapsulation and controlled release of a hydrophobic anticancer drug, doxorubicin.