Nasopharyngeal carcinoma(NPC)is a serious and highly invasive epithelial malignancy that is closely associated with Epstein‒Barr virus(EBV).Due to the lack of therapeutic vaccines for NPC,we selected EBV latent membra...Nasopharyngeal carcinoma(NPC)is a serious and highly invasive epithelial malignancy that is closely associated with Epstein‒Barr virus(EBV).Due to the lack of therapeutic vaccines for NPC,we selected EBV latent membrane protein 2(LMP2)as a preferable targeting antigen to develop a lipid-based LMP2-mRNA(mLMP2)vaccine.Full-length mLMP2 expressing LMP2 was first synthesized using an in vitro transcription method and then encapsulated into(2,3-dioleacyl propyl)trimethylammonium chloride(DOTAP)-based cationic liposomes to obtain the mRNA vaccine(LPX-mLMP2).The cell assays showed that the antigenpresenting cells were capable of highly efficient uptake of LPX-mLMP2 and expression of LMP2.LMP2 could subsequently be presented to form the peptide-major histocompatibility complex(pMHC).Furthermore,LPX-mLMP2 could accumulate in the spleen,express antigens,promote the maturation of dendritic cells and stimulate antigen-specific T-cell responses in vivo.It dramatically inhibited the tumor growth of the LMP2-expressing tumor model after three doses of vaccination.Additionally,the proliferation of antigen-specific T cells in the tumor site made a good sign for the promise of mRNA vaccines in virus-induced cancer.Overall,we provided a newly developed antigen-encoding mRNA vaccine with advantages against NPC.We also demonstrated that mRNA vaccines are attractive candidates for cancer immunotherapy.展开更多
Ocular drug delivery remains a significant challenge that is limited by poor corneal retention and permeation,resulting in low ocular bioavailability(<5%).Worse still,the most convenient and safe route of ocular dr...Ocular drug delivery remains a significant challenge that is limited by poor corneal retention and permeation,resulting in low ocular bioavailability(<5%).Worse still,the most convenient and safe route of ocular drug administration,topical administration results in a drug bioavailability of less than 1%.iRGD modified drug delivery strategies have been developed for cancer therapy,however active targeting iRGD platforms for ocular drug delivery have yet to be explored.Herein,an iRGD modified liposomes was developed for ocular drug delivery via topical administration.The results indicated that iRGD modified liposomes could prolong the corneal retention time and enhance corneal permeability in an iRGD receptor mediated manner.These findings provided a novel strategy for topical ocular drug delivery for the treatment of posterior ocular diseases.展开更多
Cancer has become a leading cause of death and constitutes an enormous burdenworldwide.Radiation is a principle treatment modality used alone or in combination with other forms of therapy,with 50%–70%of cancer patien...Cancer has become a leading cause of death and constitutes an enormous burdenworldwide.Radiation is a principle treatment modality used alone or in combination with other forms of therapy,with 50%–70%of cancer patients receiving radiotherapy at some point during their illness.It has been suggested that traditional radiotherapy(daily fractions of approximately 1.8–2 Gy over several weeks)might select for radioresistant tumor cell sub-populations,which,if not sterilized,give rise to local treatment failure and distant metastases.Thus,the challenge is to develop treatment strategies and schedules to eradicate the resistant subpopulation of tumorigenic cells rather than the predominant sensitive tumor cell population.With continued technological advances including enhanced conformal treatment technology,radiation oncologists can increasinglymaximize the dose to tumors while sparing adjacent normal tissues,to limit toxicity and damage to the latter.Increased dose conformality also facilitates changes in treatment schedules,such as changes in dose per treatment fraction and number of treatment fractions,to enhance the therapeutic ratio.For example,the recently developed large dose per fraction treatment schedules(hypofractionation)have shown clinical advantage over conventional treatment schedules in some tumor types.Experimental studies suggest that following large acute doses of radiation,recurrent tumors,presumably sustained by the most resistant tumor cell populations,may in fact be equally or more radiation sensitive than the primary tumor.In this review,we summarize the related advances in radiotherapy,including the increasing understanding of the molecular mechanisms of radioresistance,and the targeting of thesemechanisms with potent small molecule inhibitors,whichmay selectively sensitize tumor cells to radiation.展开更多
基金supported by the National Key Research and Development Program of China(No.2021YFE0206600)Sichuan Province Science and Technology Support Program(Nos.2021YFSY0008 and 2020YFH0065)+1 种基金the Translational medicine fund of West China Hospital(No.CGZH19002)1.3.5 project for disciplines of excellence,West China Hospital,Sichuan University(No.ZYGD18020/ZYJC18006).
文摘Nasopharyngeal carcinoma(NPC)is a serious and highly invasive epithelial malignancy that is closely associated with Epstein‒Barr virus(EBV).Due to the lack of therapeutic vaccines for NPC,we selected EBV latent membrane protein 2(LMP2)as a preferable targeting antigen to develop a lipid-based LMP2-mRNA(mLMP2)vaccine.Full-length mLMP2 expressing LMP2 was first synthesized using an in vitro transcription method and then encapsulated into(2,3-dioleacyl propyl)trimethylammonium chloride(DOTAP)-based cationic liposomes to obtain the mRNA vaccine(LPX-mLMP2).The cell assays showed that the antigenpresenting cells were capable of highly efficient uptake of LPX-mLMP2 and expression of LMP2.LMP2 could subsequently be presented to form the peptide-major histocompatibility complex(pMHC).Furthermore,LPX-mLMP2 could accumulate in the spleen,express antigens,promote the maturation of dendritic cells and stimulate antigen-specific T-cell responses in vivo.It dramatically inhibited the tumor growth of the LMP2-expressing tumor model after three doses of vaccination.Additionally,the proliferation of antigen-specific T cells in the tumor site made a good sign for the promise of mRNA vaccines in virus-induced cancer.Overall,we provided a newly developed antigen-encoding mRNA vaccine with advantages against NPC.We also demonstrated that mRNA vaccines are attractive candidates for cancer immunotherapy.
基金supported by the National Key S&T Special Projects(No.2018ZX09201018-024)Sichuan Province Science and Technology Plan(2019YFH0115).
文摘Ocular drug delivery remains a significant challenge that is limited by poor corneal retention and permeation,resulting in low ocular bioavailability(<5%).Worse still,the most convenient and safe route of ocular drug administration,topical administration results in a drug bioavailability of less than 1%.iRGD modified drug delivery strategies have been developed for cancer therapy,however active targeting iRGD platforms for ocular drug delivery have yet to be explored.Herein,an iRGD modified liposomes was developed for ocular drug delivery via topical administration.The results indicated that iRGD modified liposomes could prolong the corneal retention time and enhance corneal permeability in an iRGD receptor mediated manner.These findings provided a novel strategy for topical ocular drug delivery for the treatment of posterior ocular diseases.
基金The work was supported by the National Natural Science Foundation of China(Grant No.81672386)the Scitech R&D Program of Sichuan Province(2020YFS0276).
文摘Cancer has become a leading cause of death and constitutes an enormous burdenworldwide.Radiation is a principle treatment modality used alone or in combination with other forms of therapy,with 50%–70%of cancer patients receiving radiotherapy at some point during their illness.It has been suggested that traditional radiotherapy(daily fractions of approximately 1.8–2 Gy over several weeks)might select for radioresistant tumor cell sub-populations,which,if not sterilized,give rise to local treatment failure and distant metastases.Thus,the challenge is to develop treatment strategies and schedules to eradicate the resistant subpopulation of tumorigenic cells rather than the predominant sensitive tumor cell population.With continued technological advances including enhanced conformal treatment technology,radiation oncologists can increasinglymaximize the dose to tumors while sparing adjacent normal tissues,to limit toxicity and damage to the latter.Increased dose conformality also facilitates changes in treatment schedules,such as changes in dose per treatment fraction and number of treatment fractions,to enhance the therapeutic ratio.For example,the recently developed large dose per fraction treatment schedules(hypofractionation)have shown clinical advantage over conventional treatment schedules in some tumor types.Experimental studies suggest that following large acute doses of radiation,recurrent tumors,presumably sustained by the most resistant tumor cell populations,may in fact be equally or more radiation sensitive than the primary tumor.In this review,we summarize the related advances in radiotherapy,including the increasing understanding of the molecular mechanisms of radioresistance,and the targeting of thesemechanisms with potent small molecule inhibitors,whichmay selectively sensitize tumor cells to radiation.
