Multifunctional Gd-CuS loaded UCST polymeric micelles for MR/PA imaging-guided chemo-photothermal tumor treatment

Hepatocellular carcinoma(HCC)is a life-threatening disease for which there is no effective treatment currently.Novel theranostics simultaneously having excellent imaging and therapeutic functions are highly desired in cancer therapy.Herein,we develop the sialic acid(SA)modified polymeric micelles at an upper critical solution temperature(UCST)of 43℃(sialic acid-poly(ethylene glycol)-poly(acrylamide-co-acrylonitrile),SA-PEG-p(AAm-co-AN)),which further encapsulated with doxorubicin(DOX)and Gd-CuS nanoparticles(Gd-CuS NPs)for chemo-photothermal treatment of HCC guided by magnetic resonance(MR)/photoacoustic(PA)dual-mode imaging.The resultant SA-PEG-p(AAm-co-AN)/DOX/Gd-CuS(SPDG)had an excellent photothermal conversion efficiency,enabling SPDG with an instantaneous release behavior of DOX under near-infrared(NIR)irradiation.This study also revealed that SPDG could actively target to HCC,which was due to that SA had a high affinity with E-selectin overexpressed at the tumor site.Moreover,benefiting from the HCC-targeted ability and NIR light-controlled on-demand delivery of DOX,SPDG showed a superior potential in MR/PA dual-mode imaging-guided chemo-photothermal treatment.Overall,our study reveals that the designed SPDG may be used as an ideal multifunctional nanoplatform for cancer theranostics.

H_(2)O_(2)-sensitive nanoscale coordination polymers for photoacoustic tumors imaging via in vivo chromogenic assay

Photoacoustic(PA)imaging with much deeper tissue penetration and better spatial resolution had been widely employed for the prevention and diagnosis of many diseases.In this study,a new type of hydrogen peroxide(H_(2)O_(2)T-activated photoacoustic nanoprobe[Mn-AH nanoscale coordination polymer nanodots(NCPs)]was successfully synthesized by a simple one-step method in water phase containing 2,20-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)(ABTS),horse radish peroxidase(HRP),and manganese ion(Mn^(2+).After modification by polyethylene glycol(PEG),Mn-AH NCPs exhibited excellent stability and biocompatibility for in vivo H_(2)O_(2)-responsive chromogenic assay with great speci¯city and sensitivity.In the presence of H_(2)O_(2),colorless ABTS would be converted by HRP into the oxidized form with strong near-infrared(NIR)absorbance,enabling photoacoustic detection of endogenous H_(2)O_(2).Using H_(2)O_(2)-activated Mn-AH NCPs,we have successfully performed PA imaging and H_(2)O_(2)detection of subcutaneous murine colon CT26 tumor and deep-seated orthotopic bladder tumor.Due to the inherent Mn element existence inside the Mn-AH,this nanoprobe also serves as a good T1-weighted magnetic resonance imaging(MRI)contrast agent simultaneously.Lastly,after accomplishing its imaging functions,the Mn-AH NCPs could be cleared out from the body without any long-term toxicity,providing a new opportunity for cancer diagnosis and treatment.

形象哲学:中西印思想互鉴的当下思考

在形象哲学上,中西印思想有不同的思维路向,西方在实体—区分型思维中看重三维空间之form(形),由之而形成image(形象)理论;中国在虚实—关联型思维中看重四维时空之“象”,由之形成形、象、气合一的理论;印度在是—变—幻—空的思维中,看重一维时间之rūpa(色)。中西印三种思想的互鉴,对于我们在全球一体和多元互动的世界思想演进中提升对形象问题的思考,应有益处。

Optical fluence compensation for handheld photoacoustic probe:An in vivo human study case

Integrating photoacoustic(PA)and ultrasound(US)into a handheld probe to perform P A/US dual-modal imaging has been widely studied over the past few years.However,optical fuence decreases quickly in deeper tissue due to light scattering and absorption,which would signifi-cantly affect the quantitative PA imaging.In this paper,we performed a fluence compensation for a PA imaging study of human breast.The comparison of P A/US image with and without optical fuence compensation demonstrated that the fuence compensation could effectively improve imaging quality for handheld probe.

Activatable nanoscale metal-organic framework for ratiometric photoacoustic imaging of hydrogen sulfide and orthotopic colorectal cancer in vivo

Nanoscale metal-organic frameworks(nano MOFs)have emerged as a promising biomedical nanoplatform because of their unique properties.However,the exploration of nano MOFs in photoacoustic(PA)imaging is still limited.Here,a novel hydrogen sulfide(H2 S)-activated nano copper-based MOF(Cu-MOF)was developed as a near-infrared(NIR)ratiometric PA probe for in vivo monitoring of endogenous H2 S level and orthotopic colorectal cancer imaging via in situ reaction of nano Cu-MOFs with endogenous H2 S that is closely associated with tumor growth and proliferation in colon cancer.The synthesized nano Cu-MOFs displayed excellent PA responsiveness towards tumor H2 S level with high selectivity and rapid kinetics.The result suggests the developed probe may provide a unique opportunity to investigate the malignant behaviors of H2 S-associated events in vivo.

A dual-modal probe for NIR fluorogenic and ratiometric photoacoustic imaging of Cys/Hcy in vivo

Biothiols, such as cysteine(Cys) and homocysteine(Hcy), play vital roles in biological homeostasis and are closely related to various pathological and physiological processes in the living systems. Therefore, the in vivo detection of biothiols is of great importance for early diagnosis of diseases and assessment of disease progression. In this work, we developed a near-infrared(NIR) fluorescence and photoacoustic dual-modal molecular probe(NIR-S) that can be specifically activated by Cys or Hcy. The aryl-thioether substituted cyanine probe can undergo nucleophilic substitution and Smiles rearrangement reaction, resulting in specific turn-on NIR fluorescence and ratiometric photoacoustic responses for Hcy/Cys. Thus, NIR-S not only realizes the specific NIR fluorescence and photoacoustic dual mode imaging to detect Hcy/Cys in solution, but also can be applied to living cells and mice to detect Hcy/Cys. This work provided a practical tool to detect Hcy/Cys levels in vivo, which would be beneficial for the early diagnosis and progress of diseases.

Recent advances of optical imaging in animal stroke model

Stroke is a major health concern and an intensive research subject due that it is the major cause of death and the leading cause of disability worldwide. The past three decades of clinical disappointments in treating stroke must compel us to rethink our strategy. New effective protocol for stroke could greatly benefit from the advances in optical imaging technologies. This review focuses on the latest advance of applications of three optical imaging techniques in animal model of stroke, such as photoacoustic （PA） imaging, laser speckle contrast imaging （LSCI） and two-photon microscopy （TPM）. The potential roles of those techniques in the future of stroke management are also discussed.

Polyethylene glycol phospholipids encapsulated silicon 2,3-naphthalocyanine dihydroxide nanoparticles(SiNcOH-DSPE-PEG(NH2)NPs) for single NIR laser induced cancer combination therapy

Currently,the combination of photothermal therapy（PTT） and photodynamic therapy（PDT） has emerged as a powerful technique for cancer treatment.However,most examples of combined PTT and PDT reported use multi-component nanocomposites under excitation of separate wavelength,resulting in complex treatment process.In this work,a novel theranostic nanoplatform（SiNcOH-DSPE-PEG（NH2）NPs） has been successfully developed by coating silicon 2,3-naphthalocyanine dihydroxide（SiNcOH）with DSPE-PEG and DSPE-PEG-NH2 for photoacoustic（PA） imaging-guided PTT and PDT tumor ablation for the first time.The as-prepared single-agent SiNcOH-DSPE-PEG（NH2） NPs not only have good water solubility and biocompatibility,but also exhibit high photothermal conversion efficiency and singlet oxygen generation capability upon 808 nm NIR laser irradiation.In addition,owing to their high absorption at NIR region,the SiNcOH-DSPE-PEG（NH2） NPs can also be employed as an effective diagnostic nanoagent for photoacoustic（PA） imaging.In vitro and in vivo experimental results clearly indicated that the simultaneously combined PTT and PDT under the guidance of PA imaging with single NIR laser excitation can effectively kill cancer cells or eradicate tumor tissues.Taking facile synthesis and high efficiency in cancer treatment by SiNcOH-DSPE-PEG（NH2） NPs into consideration,our study provides a promising strategy to realize molecular imaging-guided combination therapy.