A cabazitaxel liposome for increased solubility, enhanced antitumor effect and reduced systemic toxicity

The potential side effects of cabazitaxel(CBZ)in the field of cancer treatment have become a great limitation to its further clinical application.Liposomal delivery is a well-established approach to increase the therapeutic index of hydrophobic drugs.In this study,a PEGmodified liposome was developed for efficiently encapsulating CBZ,thus enhancing its specific tumor inhibition effect and reducing the systemic toxicity.It was found that the loading efficiency of CBZ into the liposome could be improved with the increase of lipophilic materials,as it could be over 80%under the weight ratio of 20:1(total lipid:CBZ).The diameter of CBZ loaded liposome(CBZ@Lipo)was^100 nm.And the liposome suspending in aqueous medium was stable at 4°C for at least one month,according to the change of its size distribution.The killing ability of CBZ@Lipo to cancer cells was significantly lower comparing to that of CBZ solution,which could be attributed to the slow release of CBZ from the liposomes.However,CBZ@Lipo could induce an obvious apoptosis of the cancer cells at low concentration.Furthermore,CBZ@Lipo exhibited an expressively enhanced tumor growth inhibition effect comparing to CBZ solution.More importantly,CBZ@Lipo showed an obviously higher biosafety proved by lower hemolysis probability,stable body weight of mice during the whole experiment and no obvious lesion in histology analysis.Our work provided a useful reference of the formulation of CBZ,which had potential for greater clinical application.

Fucoidan-based dual-targeting mesoporous polydopamine for enhanced MRI-guided chemo-photothermal therapy of HCC via P-selectin-mediated drug delivery

The development of novel theranostic agents with outstanding diagnostic and therapeutic performances is still strongly desired in the treatment of hepatocellular carcinoma(HCC).Here,a fucoidan-modified mesoporous polydopamine nanoparticle dual-loaded with gadolinium iron and doxorubicin(FMPDA/Gd^(3+)/DOX)was prepared as an effective theranostic agent for magnetic resonance imaging(MRI)-guided chemo-photothermal therapy of HCC.It was found that FMPDA/Gd^(3+)/DOX had a high photothermal conversion efficiency of 33.4%and excellent T1-MRI performance with a longitudinal relaxivity(r1)value of 14.966 m M^(-1)·s^(-1).Moreover,the results suggested that FMPDA/Gd^(3+)/DOX could effectively accumulate into the tumor foci by dual-targeting the tumor-infiltrated platelets and HCC cells,which resulted from the specific interaction between fucoidan and overexpressed p-selectin receptors.The excellent tumor-homing ability and MRI-guided chemo-photothermal therapy therefore endowed FMPDA/Gd^(3+)/DOX with a strongest ability to inhibit tumor growth than the respective single treatment modality.Overall,our study demonstrated that FMPDA/Gd^(3+)/DOX could be applied as a potential nanoplatform for safe and effective cancer theranostics.

Nano transdermal system combining mitochondria-targeting cerium oxide nanoparticles with all-trans retinoic acid for psoriasis

Psoriasis is an inflammatory skin disease that is intricately linked to oxidative stress.Antioxidation and inhibition of abnormal proliferation of keratinocytes are pivotal strategies for psoriasis.Delivering drugs with these effects to the site of skin lesions is a challenge that needs to be solved.Herein,we reported a nanotransdermal delivery system composed of all-trans retinoic acid(TRA),triphenylphosphine(TPP)-modified cerium oxide(CeO2)nanoparticles,flexible nanoliposomes and gels(TCeO_(2)-TRA-FNL-Gel).The results revealed that TCeO_(2)synthesized by the anti-micelle method,with a size of approximately 5 nm,possessed excellent mitochondrial targeting ability and valence conversion capability related to scavenging reactive oxygen species(ROS).TCeO_(2)-TRA-FNL prepared by the film dispersion method,with a size of approximately 70 nm,showed high drug encapsulation efficiency(>96%).TCeO_(2)-TRA-FNL-Gel further showed sustained drug release behaviors,great transdermal permeation ability,and greater skin retention than the free TRA.The results of in vitro EGF-induced and H2O2-induced models suggested that TCeO_(2)-TRA-FNL effectively reduced the level of inflammation and alleviated oxidative stress in HaCat cells.The results of in vivo imiquimod(IMQ)-induced model indicated that TCeO_(2)-TRA-FNL-Gel could greatly alleviate the psoriasis symptoms.In summary,the transdermal drug delivery system designed in this study has shown excellent therapeutic effects on psoriasis and is prospective for the safe and accurate therapy of psoriasis.

Recent advances in nanotherapeutics for the treatment and prevention of acute kidney injury

Acute kidney injury(AKI)is a serious kidney disease without specific medications currently except for expensive dialysis treatment.Some potential drugs are limited due to their high hydrophobicity,poor in vivo stability,low bioavailability and possible adverse effects.Besides,kidney-targeted drugs are not common and small molecules are cleared too quickly to achieve effective drug concentrations in injured kidneys.These problems limit the development of pharmacological therapy for AKI.Nanotherapeutics based on nanotechnology have been proved to be an emerging and promising treatment strategy for AKI,which may solve the pharmacological therapy dilemma.More and more nanotherapeutics with different physicochemical properties are developed to efficiently deliver drugs,increase accumulation and control release of drugs in injury kidneys and also directly as effective antioxidants.Here,we discuss the recent nanotherapeutics applied in the treatment and prevention of AKI with improved effectiveness and few side effects.

Sialic acid-engineered mesoporous polydopamine nanoparticles loaded with SPIO and Fe3+as a novel theranostic agent for T1/T2 dual-mode MRI-guided combined chemo-photothermal treatment of hepatic cancer

diagnostic and therapeutic capability are highly needed for the treatment of hepatic cancer.Herein,we aimed to develop a novel mesoporous polydopamine(MPDA)-based theranostic agent for T1/T2 dual magnetic resonance imaging(MRI)-guided cancer chemo-photothermal therapy.Superparamagnetic iron oxide(SPIO)-loaded MPDA NPs(MPDA@SPIO)was firstly prepared,followed by modifying with a targeted molecule of sialic acid(SA)and chelating with Fe^(3+)(SA-MPDA@SPIO/Fe^(3+) NPs).After that,doxorubicin(DOX)-loaded SA-MPDA@SPIO/Fe^(3+) NPs(SA-MPDA@SPIO/DOX/Fe^(3+))was prepared for tumor theranostics.The prepared SAPEG-MPDA@SPIO/Fe^(3+) NPs were water-dispersible and biocompatible as evidenced by MTT assay.In vitro photothermal and relaxivity property suggested that the novel theranostic agent possessed excellent photothermal conversion capability and photostability,with relaxivity of being r1=4.29 mM1s1 and r2=105.53 mM1s1,respectively.SAPEG-MPDA@SPIO/Fe^(3+) NPs could effectively encapsulate the DOX,showing dual pH-and thermal-triggered drug release behavior.In vitro and in vivo studies revealed that SA-MPDA@SPIO/DOX/Fe^(3+) NPs could effectively target to the hepatic tumor tissue,which was possibly due to the specific interaction between SA and the overexpressed E-selectin.This behavior also endowed SA-MPDA@SPIO/DOX/Fe^(3+)NPs with a more precise T1-T2 dual mode contrast imaging effect than the one without SA modification.In addition,SAPEG-MPDA@SPIO/DOX/Fe^(3+) NPs displayed a superior therapeutic effect,which was due to its active targeting ability and combined effects of chemotherapy and photothermal therapy.These results demonstrated that SAPEG-MPDA@SPIO/DOX/Fe^(3+) NPs is an effective targeted nanoplatform for tumor theranostics,having potential value in the effective treatment of hepatic cancer.

Thermo-sensitive micelles extend therapeutic potential for febrile seizures

Dear Editor,Febrile seizures(FS)are common convulsive disorder induced by fever,affecting up to 5% of children under the age of 5 years.Although FS are characterized by their benign prognosis,children with complex FS,in the condition with recurrent or prolonged seizures,are at high risks of temporal lobe epilepsy in later life.1 Currently,there is no appropriate pharmacotherapeutic option to control FS,and later epileptogenesis in the perspective of both therapeutic efficacy and safety.

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.