Self‐Assembling Endogenous Biliverdin as a Versatile Near‐Infrared Photothermal Nanoagent for Cancer Theranostics

Photothermal nanomaterials that integrate multimodal imaging and therapeutic functions provide promising opportunities for noninvasive and targeted diagnosis and treatment in precision medicine. However, the clinical translation of existing photothermal nanoagents is severely hindered by their unclear physiological metabolism, which makes them a strong concern for biosafety. Here, the utilization of biliverdin (BV), an endogenic near‐infrared (NIR)‐absorbing pigment with well‐studied metabolic pathways, to develop photothermal nanoagents with the aim of providing efficient and metabolizable candidates for tumor diagnosis and therapy, is demonstrated. It is shown that BV nanoagents with intense NIR absorption, long‐term photostability and colloidal stability, and high photothermal conversion efficiency can be readily constructed by the supramolecular multicomponent self‐assembly of BV, metal‐binding short peptides, and metal ions through the reciprocity and synergy of coordination and multiple noncovalent interactions. In vivo data reveal that the BV nanoagents selectively accumulate in tumors, locally elevate tumor temperature under mild NIR irradiation, and consequently induce efficient photothermal tumor ablation with promising biocompatibility. Furthermore, the BV nanoagents can serve as a multimodal contrast for tumor visualization through both photoacoustic and magnetic resonance imaging. BV has no biosafety concerns, and thereby offers a great potential in precision medicine by integrating multiple theranostic functions.     

Self‐Assembled Peptide‐ and Protein‐Based Nanomaterials for Antitumor Photodynamic and Photothermal Therapy

Tremendous interest in self‐assembly of peptides and proteins towards functional nanomaterials has been inspired by naturally evolving self‐assembly in biological construction of multiple and sophisticated protein architectures in organisms. Self‐assembled peptide and protein nanoarchitectures are excellent promising candidates for facilitating biomedical applications due to their advantages of structural, mechanical, and functional diversity and high biocompability and biodegradability. Here, this review focuses on the self‐assembly of peptides and proteins for fabrication of phototherapeutic nanomaterials for antitumor photodynamic and photothermal therapy, with emphasis on building blocks, non‐covalent interactions, strategies, and the nanoarchitectures of self‐assembly. The exciting antitumor activities achieved by these phototherapeutic nanomaterials are also discussed in‐depth, along with the relationships between their specific nanoarchitectures and their unique properties, providing an increased understanding of the role of peptide and protein self‐assembly in improving the efficiency of photodynamic and photothermal therapy.     

Structural‐Engineering Rationales of Gold Nanoparticles for Cancer Theranostics

Personalized theranostics of cancer is increasingly desired, and can be realized by virtue of multifunctional nanomaterials with possible high performances. Gold nanoparticles (GNPs) are a type of especially promising candidate for cancer theranostics, because their synthesis and modification are facile, their structures and physicochemical properties are flexibly controlled, and they are also biocompatible. Especially, the localized surface plasmon resonance and multivalent coordination effects on the surface endow them with NIR light‐triggered photothermal imaging and therapy, controlled drug release, and targeted drug delivery. Although the structure, properties, and theranostic application of GNPs are considerably plentiful, no expert review systematically explains the relationships among their structure, property. and application and induces the engineering rationales of GNPs for cancer theranostics. Hence, there are no clear rules to guide the facile construction of optimal GNP structures aiming at a specific theranostic application. A series of structural‐engineering rationales of GNPs for cancer theranostics is proposed through digging out the deep relationships between the structure and properties of GNPs. These rationales will be inspiring for guiding the engineering of specific and advanced GNPs for personalized cancer theranostics.     

Light‐Responsive Biodegradable Nanorattles for Cancer Theranostics

Cancer nanotheranostics, integrating both diagnostic and therapeutic functions into nanoscale agents, are advanced solutions for cancer management. Herein, a light‐responsive biodegradable nanorattle‐based perfluoropentane‐(PFP)‐filled mesoporous‐silica‐film‐coated gold nanorod (GNR@SiO₂‐PFP) is strategically designed and prepared for enhanced ultrasound (US)/photoacoustic (PA) dual‐modality imaging guided photothermal therapy of melanoma. The as‐prepared nanorattles are composed of a thin mesoporous silica film as the shell, which endows the nanoplatform with flexible morphology and excellent biodegradability, as well as large cavity for PFP filling. Upon 808 nm laser irradiation, the loaded PFP will undergo a liquid–gas phase transition due to the heat generation from GNRs, thus generating nanobubbles followed by the coalescence into microbubbles. The conversion of nanobubbles to microbubbles can improve the intratumoral permeation and retention in nonmicrovascular tissue, as well as enhance the tumor‐targeted US imaging signals. This nanotheranostic platform exhibits excellent biocompatibility and biodegradability, distinct gas bubbling phenomenon, good US/PA imaging contrast, and remarkable photothermal efficiency. The results demonstrate that the GNR@SiO₂‐PFP nanorattles hold great potential for cancer nanotheranostics.     

Self‐Assembled Biomimetic Capsules for Self‐Preservation

The inorganic semiconductor is an attractive material in sewage disposal and solar power generation. The main challenges associated with environment‐sensitive semiconductors are structural degradation and deactivation caused by the unfavorable environment. Here, inspired by the pomegranate, a self‐protection strategy based on the self‐assembly of silver chloride (AgCl) particles is reported. The distributed photosensitive AgCl particles can be encapsulated by themselves through mixing aqueous silver nitrate and protic ionic liquids (PILs). A probable assembling mechanism is proposed based on the electrostatic potential investigation of PILs cations. The AgCl particles inside the shell maintain their morphology and structure well after 6 months light‐treatment. Moreover, they exhibit excellent photocatalytic activity, same as newly prepared AgCl particles, for degradation of methyl orange (MO), neutral red (NR), bromocresol green (BG), rhodamine B (RhB), Congo red (CR), and crystal violet (CV).     

Flexible Photothermal Assemblies with Tunable Gold Patterns for Improved Imaging‐Guided Synergistic Therapy

Self‐assembly of gold nanoparticles demonstrates a promising approach to realize enhanced photoacoustic imaging (PAI) and photothermal therapy (PTT) for accurate diagnosis and efficient cancer therapy. Herein, unique photothermal assemblies with tunable patterns of gold nanoparticles (including arcs, rings, ribbons, and vesicles) on poly(lactic‐co‐glycolic acid) (PLGA) spheres are constructed taking advantage of emulsion‐confined and polymer‐directed self‐assembly strategies. The influencing factors and formation mechanism to produce the assemblies are investigated in details. Both the emulsion structure and migration behaviors of amphiphilic block copolymer tethered gold nanoparticles are found to contribute to the formation of versatile photothermal assemblies. Hyaluronic acid‐modified R‐PLGA‐Au (RPA) exhibits outstanding photothermal performances under NIR laser irradiation, which is induced by strong plasmonic coupling between adjacent gold nanoparticles. It is interesting that secondary assembly of RPA can be triggered by NIR laser irradiation. Prolonged residence time in tumors is achieved after RPA assemblies are fused into superstructures with larger sizes, realizing real‐time monitoring of the therapeutic processes via PAI with enhanced photoacoustic signals. Notably, synergistic effect resulting from PTT‐enhanced chemotherapy is realized to demonstrate high antitumor performance. This work provides a facile strategy to construct flexible photothermal assemblies with favorable properties for imaging‐guided synergistic therapy.     

Controlled Gold Nanorod Reorientation and Hexagonal Order in Micromolded Gold Nanorod@pNIPAM Microgel Chain Arrays

A one‐step soft lithography based pathway to manufacture aligned gold nanorod@poly‐(N‐isopropylacrylamide) (GNR@pNIPAM) hybrid chains with hexagonal arrangement of the nanorods and with an anisotropic optical response is presented. After demonstration of an efficient synthesis protocol, yielding uniform composite microgels in high concentration, a micromolding procedure using wrinkled polydimethylsiloxane (PDMS) templates to fabricate aligned hybrid chains is introduced. It is found that the self‐assembled GNR@pNIPAM microgels inside the PDMS wrinkle grooves can be transferred onto solid substrates, on which they exhibit a hexagonal order, as confirmed by small‐angle X‐ray scattering. Further, it is shown that the application of minimized PDMS wrinkle dimensions aligns GNRs inside the pNIPAM microgels, and that the optical response of such molded assemblies is anisotropic.