Gold nanocages as multifunctional materials for nanomedicine

Featured by tunable localized surface plasmon resonance peaks in the near-infrared region and hollow interiors, Au nanocages represent a novel class of multifunctional nanomat, erials that have gained considerable attention in recent vears. This short review summarizes our recent work on the capabilities of An nanocages in nanomedicine. We start with a brief description of the synthesis of Au nanocages and highlight our recent protocols for the scaled-up production of An na.nocages. We then use a numer of examples to illustrate how Au nanocages can contribute to nanomedicine with respect to both diagnosis and therapy.

Ultra-fast microwave aided synthesis of gold nanocages and structural maneuver studies

Gold nanocages （AuNcgs） are well-studied, hollow, metallic nanostructures that have fascinated researchers in the fields of nanotechnology, materials science, photoelectronics, biotechnology, and medical science for the last decade. However, the time-consuming synthesis of AuNcgs has limited their widespread use in materials science and nano-biotechnology. A novel, ultra-fast, simple, and highly convenient method for the production of AuNcgs using microwave heating is demonstrated herein. This quick method of AuNcg synthesis requires mild laboratory conditions for large-scale production of AuNcgs. The microwave heating technique offers the advantage of precise mechanical control over the temperature and heating power, even for the shortest reaction period （i.e., seconds）. Microwave-synthesized AuNcgs were compared with conventionally synthesized AuNcgs. Structural maneuver studies employing the conventionally produced AuNcgs revealed the formation of screw dislocations and a shift in the lattice plane. Detailed characterization of the microwave-generated AuNcgs was performed using high resolution transmission electron microscopy （HRTEM）, scanning electron microscopy （SEM）, X-ray powder diffraction （XRD）, and spectroscopic techniques.

Gold nanocages in cancer diagnosis,therapy,and theranostics:A brief review

Regarding the increasing number of cancer patients,the global burden of this disease is continuing to grow.Despite a considerable improvement in the diagnosis and treatment of various types of cancer,new diagnosis and treatment strategies are required.Nanotechnology,as an interesting and advanced field in medicine,is aimed to further advance both cancer diagnosis and treatment.Gold nanocages(AuNCs),with hollow interiors and porous walls,have received a great deal of interest in various biomedical applications such as diagnosis,imaging,drug delivery,and hyperthermia therapy due to their special physicochemical characteristics including the porous structure and surface functionalization as well as optical and photothermal properties.This review is focused on recent developments in therapeutic and diagnostic and applications of AuNCs with an emphasis on their theranostic applications in cancer diseases.

Dual-Wavelength Photosensitive Nano-in-Micro Scaffold Regulates Innate and Adaptive Immune Responses for Osteogenesis

The immune response of a biomaterial determines its osteoinductive effect.Although the mechanisms by which some immune cells promote regeneration have been revealed,the biomaterial-induced immune response is a dynamic process involving multiple cells.Currently,it is challenging to accurately regulate the innate and adaptive immune responses to promote osteoinduction in biomaterials.Herein,we investigated the roles of macrophages and dendritic cells(DCs)during the osteoinduction of biphasic calcium phosphate(BCP)scaffolds.We found that osteoinductive BCP directed M2 macrophage polarization and inhibited DC maturation,resulting in low T cell response and efficient osteogenesis.Accordingly,a dual-targeting nano-in-micro scaffold(BCP loaded with gold nanocage,BCP-GNC)was designed to regulate the immune responses of macrophages and DCs.Through a dual-wavelength photosensitive switch,BCP-GNC releases interleukin-4 in the early stage of osteoinduction to target M2 macrophages and then releases dexamethasone in the later stage to target immature DCs,creating a desirable inflammatory environment for osteogenesis.This study demonstrates that biomaterials developed to have specific regulatory capacities for immune cells can be used to control the early inflammatory responses of implanted materials and induce osteogenesis.

Combination of anti-inflammatory therapy and RNA interference by light-inducible hybrid nanomedicine for osteoarthritis treatment

Osteoarthritis(OA)is a type of highly prevalent heterogeneous degenerative disease that leads to joint pain,deformity,the destruction of articular cartilage,and eventual disability.The current treatment strategies for OA often suffer from systemic side effects,poor anti-inflammatory efficacy,and persistent pain.To address these issues,we develop light-inducible nanomedicine that enables the co-delivery of anti-inflammatory drug(diacerein,DIA)and small interfering RNA(siRNA)targeting nerve growth factor(NGF)for pain relief to enhance the therapeutic efficacy of OA.The nanomedicine is based on poly(β-amino-ester)-coated gold nanocages(AuNCs),which is further incorporated with the phase-change material(lauric acid/stearic acid,LA/SA).Following intra-articular(IA)injection in vivo,the nanomedicine displays high degree of drug accumulation and retention in the joint lesion of OA mouse models.The photothermal effect,induced by AuNCs,not only promotes DIA and siRNA release,but also upregulates the expression of heat shock protein 70(HSP-70)to resist the apoptosis of chondrocytes in the inflammatory condition.The internalization of both DIA and siRNA results in strong anti-inflammatory and pain-relieving effects,which greatly contribute to the joint repair of OA mice.This study offers a promising combination strategy for OA treatment.

Microwave triggered multifunctional nanoplatform for targeted photothermal-chemotherapy in castration-resistant prostate cancer

Lacking a precise targeting strategy,castration-resistant prostate cancer(CRPC)is still hard to be treat effectively.Exploring treatment options that can accurately target CPRC is an important issue with urgent need.In this study,a novel nanotechnologybased strategy had been developed for the precise target treatment of CRPC.By combining microwaves and photothermal therapy(PTT),this nanoplatform,cmHSP70-PL-AuNC-DOX,targets tumor tissues with outstanding precision and achieves better anti-tumor activity by simultaneously eliciting photothermal and chemotherapeutic effects.From nanotechnology,cmHSP70-modified and thermo-sensitive liposome-coated AuNC-DOX were prepared and used for CRPC-targeted photothermal ablation and chemotherapy.Doxorubicin(DOX)was selected as the chemotherapeutic agent for cytotoxicity.In terms of the curative scheme,prostate tissues were firstly pre-treated with microwaves to induce the expression of heat shock protein 70(HSP70)and its migration to the cell membrane,which was then targeted by HSP70 antibody(cmHSP70)coated on the nanoparticles to achieve accurate drug delivery.The nanoplatform then achieved precise ablation and controlled release of DOX under external near-infrared(NIR)irradiation.Through the implementation,the targeting,cell killing,and safety of this therapeutical strategy had been verified in vivo and in vitro.This work establishes an accurate,controllable,efficient,non-invasive,and safe treatment platform for targeting CRPC,provides a rational design for CRPC’s PTT,and offers new prospects for nanomedicines with great precision.