化學療法被廣泛運用於治療癌症，但注射化療藥物後藥物沒有專一性地分佈於體內造成副作用。因此，可以利用藥物傳遞系統增加藥物的專一性以及藥物在腫瘤處的累積量以達到更良好的治療效果。聚胺酸類的高分子可在溶液中自組裝因為其具有特殊的二級結構，當其裝載藥物時，可藉由調控外界刺激控制藥物的釋放。本研究合成聚乙二醇-聚賴胺酸-聚酪胺酸高分子，並利用DTSSP交聯劑引入雙硫鍵，形成具酸鹼/氧化還原敏感之聚胺酸類微胞。利用此微胞包覆阿黴素形成粒徑約63奈米且載藥率約為16.5%的載體。利用穿透式電子顯微鏡觀察發現此微胞在pH 7.4的環境下呈現均一的球形，然而已交聯的微胞在模擬腫瘤組織的酸性(pH 5.0)以及具高氧化還原物質(GSH 10mM)的環境中呈現不規則聚集且降解的情形。體外實驗中發現，對於路易士肺癌細胞未利用載體所包覆的阿黴素相較於載藥之微胞具有較高的細胞毒性，但載藥之微胞可以減低DOX對於纖維母細胞的毒性。此外，在增生實驗中發現此載藥之微胞能有效且選擇性抑制路易士肺癌細胞的增生，此現象在模擬腫瘤環境的酸性培養液中更為顯著。體內實驗中在皮下路易士腫瘤小鼠模型中，證實此載藥之微胞比起未利用載體所包覆的阿黴素更具腫瘤抑制效果並且降低藥物的副作用，進一步證實利用聚乙二醇-聚賴胺酸-聚酪胺酸高分子包覆阿黴素有利於增進化療藥物的療效，在癌症治療應用上具有潛力。

Nanocarriers are promising to benefit cancer therapy. Stimuli-responsive polypeptide-based copolymers can self-assemble in solution, and release their payloads under specific stimuli due to their specific secondary structure. To enhance site-specific drug release in tumor tissues and the antitumor efficacy of antitumor agents, pH/redox-responsive poly(ethylene glycol)-b-poly(L-lysine-co-L-tyrosine) copolymer (PEG-b-(Lys-co-Tyr)) was developed to encapsulate doxorubicin (DOX) and cross-link with 3,3’-dithiobis(sulfosuccinimidylpropionate) (DTSSP). The DOX-loaded assemblies had diameters around 63 nm and a superior drug-loading content (DLC) (~16.5%). Under TEM observation, polypeptide assemblies showed uniformly spherical morphologies in pH 7.4 environment; however, cross-linked polypeptide assemblies demonstrated redox-triggered degradation and amorphous aggregates in pH 5.0 and GSH (10 mM) conditions. Cytotoxicity studies showed that free DOX was more toxic than DOX-loaded assemblies against LLC cells; however, DOX-loaded assemblies decreased the burden of DOX on NIH3T3 cells. The cell uptake level of free DOX was slightly higher than that of DOX-loaded assemblies. Proliferation assay showed that DOX-loaded assemblies can selectively inhibit Lewis lung carcinoma (LLC) cells proliferation especially in acidic environment. Moreover, in vivo studies validated that DOX-loaded assemblies showed significant antitumor efficacy on LLC cells subcutaneous model and reduced the side effects, indicating its great potential for cancer treatments.

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