Peptide self-assemblies with multiple nanostructures have great potentials in functional biomaterials, and yet the tedious and costly covalent peptide modification and the lack of facile controllability on self-assembly morphology retard the peptide-related exploration. Here we report a simple approach to fabricate a supramolecular peptide that shows programmable self-assembly with multiple morphologies and application in photodynamic therapy. Pillar[5]arene-based host−guest recognition is used to construct a supramolecular peptide, which simplify the peptide modification and promote the controllability of the self-assembly behavior. Due to the ERGDS sequences on the exterior surfaces and hydrophobic cores of self-assemblies, the nanoparticles formed from the supramolecular peptide are suitable vehicles to encapsulate a photosensitizer for photodynamic therapy. In vitro and in vivo studies demonstrate that the inherent targeting capability and supramolecular strategy greatly boost its photodynamic therapeutic efficiency. This supramolecular peptide holds promising potentials in precise cancer therapy and perspectives for the peptide modification.

Oxidative stress and inflammation are at the root of a multitude of diseases. Treatment of these conditions is often necessary but current standard therapies to fight excessive reactive oxygen species (ROS) and inflammation are often ineffective or complicated by substantial safety concerns. Nanozymes are emerging nanomaterials with intrinsic enzyme‐like properties that hold great promise for effective cancer treatment, bacterial elimination, and anti‐inflammatory/anti‐oxidant therapy. While there is rapid progress in tailoring their catalytic activities as evidenced by the recent integration of single‐atom catalysts (SACs) to create next‐generation nanozymes with superior activity, selectivity, and stability, a better understanding and tuning of their safety profile is imperative for successful clinical translation. This review outlines the current applied safety assessment approaches and provides a comprehensive summary of the safety knowledge of therapeutic nanozymes. Overall, nanozymes so far show good in vitro and in vivo biocompatibility despite considerable differences in their composition and enzymatic activities. However, current safety investigations mostly cover a limited set of basic toxicological endpoints, which do not allow for a thorough and deep assessment. Ultimately, remaining research gaps that should be carefully addressed in future studies are highlighted, to optimize the safety profile of therapeutic nanozymes early in their pre‐clinical development.

The widely used bovine serum albumin (BSA) nanoparticles (NPs) were modified with poly(allylamine hydrochloride) (PAH)/sodium poly(4-styrene sulfonate) (PSS) multilayers and aptamers to improve their suspension stability and targeting ability. For this to occur, a PAH-g-poly(ethylene glycol) (PAH-g-PEG–COOH) layer was further adsorbed onto the (PAH/PSS)₂ multilayer-coated BSA NPs and used to covalently bond the aptamer AS1411, which is known to specifically bind the over-expressed nucleolin on cancer cell membranes. The PEGylated multilayer-coated BSA NPs showed good suspension stability in diverse media, in particular in a serum containing medium. By a mechanism of spontaneous deposition, doxorubicin (DOX) was effectively loaded into the pre-formed BSA NPs with both good encapsulation efficiency (98.6%) and loading percentage (9%). The loaded drug showed a pH-dependent release behaviour, i.e. faster at pH 5.5 than at pH 7.4. The multilayer coating did not significantly influence either both drug loading or release. In vitro cell culture demonstrated that the as-prepared BSA NPs could be specifically delivered to liver cancer cells, leading to higher cellular uptake and cytotoxicity.