Ukuhanjiswa kweziyobisi okuJolisiweyo kuMhlaza

Ukuhanjiswa kweziyobisi okuJolisiweyo kuMhlaza ijolise ekuphuculeni ukusebenza konyango kunye nokunciphisa imiphumo emibi ngokuhambisa ii-agent zonyango ngokukodwa kwiiseli zomhlaza, ngelixa unciphisa ukubonakaliswa kwezicubu eziphilileyo. Le ndlela isebenzisa izicwangciso ezahlukeneyo, kuquka i-nanoparticles, i-antibodies, kunye ne-peptides, ukukhetha ngokukhetha iiseli zomhlaza kunye nokukhupha amachiza kwindawo ye-tumor. Olu nikezelo lugxininisiweyo luphucula ukuxinana kweziyobisi ngaphakathi kwethumba, lukhokelela kwiziphumo eziphuculweyo kunye nokunciphisa ubutyhefu benkqubo. Ukuhanjiswa kweziyobisi okuJolisiweyo kuMhlaza. Injongo ephambili ye Ukuhanjiswa kweziyobisi okuJolisiweyo kuMhlaza kukwandisa isiphumo sonyango lwamachiza ngelixa unciphisa iziphumo zabo ezinobungozi obunobungozi kwiiseli eziphilileyo. Oku kuphunyezwa ngokuzisa amachiza ngqo kwindawo yethumba okanye iiseli zomhlaza, ukuqinisekisa ukuba umphumo wechiza ugxininiswe apho ufuneka kakhulu. Nge IZiko loPhando ngoMhlaza laseShandong Baofa, sizinikele ekuqhubeleni phambili eli candelo ngophando olutsha kunye nezicelo zeklinikhi.Kutheni kubalulekile ukuhanjiswa kwechiza okuJolisiweyo? Ichemotherapy yesintu ihlala ibandakanya ulawulo lwenkqubo lwamachiza, okuthetha ukuba amachiza ajikeleza kuwo wonke umzimba. Oku kunokukhokelela kwiziphumo ebezingalindelekanga ezibalulekileyo, ezinjengokulahleka kweenwele, isicaphucaphu, kunye nokunyanzelwa kokhuselo lomzimba, njengoko iiseli ezisempilweni zikwachatshazelwa ngamachiza echemotherapy. Ukuhanjiswa kweziyobisi okuJolisiweyo kuMhlaza inika iingenelo ezininzi eziphambili: Iziphumo ebezingalindelekanga eziNcitshisiweyo: Ngokujolisa iiseli zomhlaza ngokuthe ngqo, iiseli ezisempilweni ziyasinda, ezikhokelela kwiziphumo ebezingalindelekanga ezimbalwa nezincinci. Ukusebenza okuphuculweyo: Uxinzelelo oluphezulu lwechiza lunokuhanjiswa ngokuthe ngqo kwindawo ye-tumor, ukuphucula ukusebenza kwayo. IziPhumo zeSigulana ezomeleziweyo: Ukusebenza ngcono kunye neziphumo ebezingalindelekanga ezincitshisiweyo kunokukhokelela ekuphuculweni komgangatho wobomi kunye namazinga okusinda jikelele kwizigulane ezinomhlaza. Ukoyisa ukuxhathisa iziyobisi: Unikezelo ekujoliswe kulo lunokunceda ukoyisa iindlela zokuxhathisa amachiza ezinokuphuhliswa ziiseli zomhlaza ngokuhamba kwexesha.Amaqhinga oNikezelo lwechiza ekuJolisiweyoIzicwangciso eziliqili ezisetyenziswayo Ukuhanjiswa kweziyobisi okuJolisiweyo kuMhlaza, nganye inesixhobo sayo esikhethekileyo sokujolisa ngokukhethiweyo kwiiseli zomhlaza: iPassive TargetingPassive targeting ixhomekeke kwiimpawu ezizodwa zezicubu zethumba, ezifana nemithambo yegazi evuzayo kunye nokuphazamiseka kwe-lymphatic drainage. Iinanoparticles zenzelwe ukuxhaphaza ezi mpawu, ziqokelele ngokukhethekileyo kwi-tumor microenvironment. Oku kukwabizwa ngokuba yi-Enhance Permeability and Retention (EPR) isiphumo.Ukujoliswa okusebenzayo okusebenzayo kubandakanya ukuguqula abathwali beziyobisi kunye nee-ligands ezithile, ezifana ne-antibodies, i-peptides, okanye i-aptamers, ezibophelela kwi-receptors echazwe ngokugqithiseleyo kwiiseli zomhlaza. Olu nxibelelwano luququzelela ukuthatyathwa okukhethiweyo komthuthi weziyobisi ngeeseli zomhlaza. Le ndlela ibandakanya:Ii-Antibody-Drug Conjugates (ADCs)ADCs zine-antibody eqaphela ngokukodwa i-antigen enxulumene nethumba, edityaniswe neyeza elinamandla le-cytotoxic. Emva kokuba i-ADC ibophe kwiseli yomhlaza, ifakwe ngaphakathi, kwaye iyeza likhutshwa ngaphakathi kwiseli, elikhokelela ekufeni kweeseli. Umzekelo yi-Ado-Trastuzumab Emtansine (Kadcyla) ejolise kwiiseli zomhlaza webele ze-HER2 [1].I-Ligand-Receptor Interactions Iiseli zomhlaza zihlala zigqithisa ii-receptors ezithile kumphezulu wazo. Ngokuncamathisela ii-ligands (iimolekyuli ezibophelela kwezi zamkeli) kubathwali bamachiza, kuyenzeka ukuba kujongwe ichiza ngokuthe ngqo kwezi seli zomhlaza. I-Folate receptors kunye ne-transferrin receptors ziithagethi eziqhelekileyo [2] .I-Stimuli-Responsive DeliveryStimuli-responsive delivery systems zenzelwe ukukhulula iziyobisi kuphela xa zibangelwa yi-stimuli ethile ekhoyo kwi-tumor microenvironment, njengokutshintsha kwe-pH, umsebenzi we-enzyme, okanye i-redox. Oku kuqinisekisa ukuba ichiza likhutshwa kuphela kwindawo yethumba, kuncitshiswe iziphumo ebekujoliswe kuzo. Imizekelo iquka ukusebenzisa ii-liposomes ezivakalelwa nge-pH ezikhulula umthwalo wazo kwindawo ene-acidic yamathumba [3]. Ukuhanjiswa kweziyobisi okuJolisiweyo kuMhlaza. La masuntswana mancinci, aqala ukusuka kwi-1 ukuya kwi-nanometers ye-100 ngobukhulu, anokwenziwa ubunjineli bokuthwala amachiza kwaye ngokukhetha awase kwiiseli zomhlaza. Iindidi ezahlukeneyo ze-nanoparticles zisetyenziswa, nganye ineengenelo zayo: I-Liposomes: I-Spherical vesicles eyenziwe nge-lipid bilayers, i-liposomes inokubamba zombini izidakamizwa ze-hydrophilic kunye ne-hydrophobic. IiNanoparticles zePolymeric: Yenziwe kwiipolymers ze-biodegradable, ezi nanoparticles zibonelela ngokukhutshwa kweziyobisi ezilawulwayo kunye nokuzinza okuphuculweyo. Amachaphaza e-Quantum: I-nanocrystals ye-Semiconductor eneempawu ezikhethekileyo ze-optical, amachaphaza e-quantum angasetyenziselwa ukucinga kunye nokuhanjiswa kweziyobisi. IiNanotubes zeCarbon: Izakhiwo ze-Cylindrical ezenziwe ngama-athomu ekhabhoni, i-carbon nanotubes inokusebenza ngokujoliswa kwe-ligands kunye neziyobisi. Ukuhanjiswa kweziyobisi okuJolisiweyo kuMhlaza Iinkqubo okwangoku zisetyenziswa ekliniki okanye ziphantsi kophuhliso: I-Doxil/Caelyx: I-Liposomal doxorubicin, evunyiweyo kunyango lomhlaza we-ovarian, i-Kaposi's sarcoma, kunye ne-myeloma eninzi [4]. Ukuqulunqwa kwayo kwe-liposomal kunciphisa i-cardiotoxicity xa kuthelekiswa ne-doxorubicin yendabuko. Abraxane: I-Albumin-bound paclitaxel, esetyenziselwa ukunyanga umhlaza wamabele, umhlaza wemiphunga ongeyonxalenye encinci, kunye nomhlaza wepancreatic [5]. Ukubophelela kwe-albumin kwandisa ukuhanjiswa kweziyobisi kwindawo ye-tumor.Imingeni kunye nezikhokelo zexesha elizayoWhile Ukuhanjiswa kweziyobisi okuJolisiweyo kuMhlaza unesithembiso esikhulu, imingeni emininzi isasele: I-Tumor Heterogeneity: Iiseli zomhlaza ngaphakathi kwethumba zinokubonisa iimpawu ezahlukeneyo, okwenza kube nzima ukujolisa zonke iiseli ngokufanelekileyo. Ukumelana neziyobisi: Iiseli zomhlaza zinokukhula ukuxhathisa kunyango olujoliswe kuyo ngokuhamba kwexesha. Izithintelo zohambiso: Ukufikelela kwindawo ye-tumor kunokuba ngumngeni ngenxa yezithintelo zomzimba, ezifana nomqobo wegazi-ubuchopho. Ukwandiswa kunye nokuVeliswa: Ukuvelisa iinkqubo ezijoliswe ekunikezelweni kweziyobisi kumlinganiselo omkhulu kunokuba nzima kwaye kuyabiza.Iinzame zophando lwexesha elizayo zijoliswe: Ukuphuhlisa izicwangciso ezijoliswe kuzo eziphucukileyo zokoyisa i-tumor heterogeneity. Ukudibanisa unyango olujoliswe kuyo kunye nezinye iindlela zonyango, ezifana ne-immunotherapy. Ukudala iinkqubo zokuhanjiswa kwe-stimuli ezinokuziqhelanisa nokutshintsha kwe-tumor microenvironment. Ukuphucula ubungakanani kunye nokusebenza kakuhle kweendleko zokwenziwa kweenkqubo ekujoliswe kuzo zokuhanjiswa kweziyobisi. Indima yeShandong Baofa Cancer Research InstituteAt. IZiko loPhando ngoMhlaza laseShandong Baofa, sithatha inxaxheba ngokukhutheleyo kuphando kunye nophuhliso lwenoveli Ukuhanjiswa kweziyobisi okuJolisiweyo kuMhlaza iinkqubo. Iqela lethu lezenzululwazi kunye noogqirha basebenzela ukoyisa le mingeni ikhankanywe ngasentla kwaye baguqulela iziphumo zophando ezithembisayo kwizicelo zeklinikhi. Siyayikholelwa loo nto Ukuhanjiswa kweziyobisi okuJolisiweyo kuMhlaza sisicwangciso esiphambili sokuphucula iziphumo zonyango lomhlaza kunye nokuphucula umgangatho wobomi kwizigulane ezinomhlaza.IsipheloUkuhanjiswa kweziyobisi okuJolisiweyo kuMhlaza imele ukuqhubela phambili okubonakalayo kunyango lomhlaza, inika amandla okuphucula ukusebenza kunye nokunciphisa iziphumo ebezingalindelekanga. Ngokujolisa ngokukhetha iiseli zomhlaza, ezi nkqubo zinokuzisa ugxininiso oluphezulu lwamachiza ngqo kwindawo yethumba, ekhokelela kwiziphumo ezingcono kwizigulana. Ngelixa imingeni isekhona, uphando oluqhubekayo kunye neenzame zophuhliso zivula indlela yonyango olusebenzayo kunye nolomntu ngamnye. National Cancer Institute - Antibody-Drug Conjugates Ukujolisa i-folate receptor kunyango lomhlaza liposomes pH-sensitive kunyango lomhlaza. I-Arhente yaMayeza yaseYurophu - iDoxil FDA - Abraxane Prescribing Information