白细胞介素-2脂质体的制备及其抗肿瘤作用

The preparation and antitumor effects of interleukin-2 liposomes

目的：研究白细胞介素－２（ＩＬ－２）脂质体对小鼠Ｂ－１６黑色素瘤肺转移瘤的抑瘤活性和对荷瘤鼠脾淋巴细胞增殖的影响。方法：改良薄膜—超声法制备ＩＬ－２脂质体；正常及免疫受抑的Ｂ－１６黑色素瘤肺转移Ｃ５７ＢＬ／６Ｎ小鼠ｉｐ游离（０．２～５×１０４ｕ／ｋｇ·ｄ×１０ｄ）或脂质体包封的ＩＬ－２（０．０４～１．０×１０４ｕ／ｋｇ·ｄ×１０ｄ），检测肺湿重、肺转移结节数和脾淋巴细胞３Ｈ－ＴｄＲ掺入量。结果：制备的ＩＬ－２脂质体为直径２００～２５００ｎｍ的大单层脂质体，包封率４８．２％。ＩＬ－２脂质体可使荷瘤鼠肺湿重下降０．４％～１３．１％，肺转移结节减少２．７～４３．５％，脾细胞３Ｈ－ＴｄＲ掺入量增加１．０５～１．９０倍，其效应相当于５倍量的游离ＩＬ－２，对免疫受抑荷瘤鼠的作用更强（Ｐ＜０．０１）。结论：ＩＬ－２脂质体对小鼠Ｂ－１６黑色素瘤肺转移瘤有显著的抑瘤活性，促进脾淋巴细胞的增殖，活性约相当于５倍量的游离ＩＬ－２。

Aims: To study the effects of liposome-encapsulated interleukin-2 (IL-2) on murine pulmonary metastases of B-16 melanoma and the proliferation of splenocytes in the mice. Methods: IL-2 liposomes were prepared using a improved dried film-ultrasonic procedure. Normal or immunosuppressed C57 BL/6N mice with B-16 melanoma pulmonary metastases were administrated by once-daily ip injection of free IL-2 (0.2～5.0×104 u/kg·d) or IL-2 liposomes (0.04～1.0×104 u/kg·d) for 10 d. The lung weight, numbers of pulmonary metastases foci and 3H-TdR incorporation of splenocytes of the mice were determined. Results: IL-2 liposomes synthesized were large unilamellar vesicles (200～2500 nm) with 48.2% of entrapmen were prepared. The antitumor effects of IL-2 liposomes were expressed as decrease of lung weight (0.4%～13.1%) and reduced numbers of pulmonary metastases (2.7%～43.5%), the incorporated radioactivity of splenocytes was increased by 1.05～1.90 folds, and the similar effects of antitumor and promoted splenocytic proliferation was taken in 5-time dose of free IL-2. IL-2 liposomes had significantly superior efficacy in immunosuppressed tumor-bearing mice (P<0.01). Conclusions: IL-2 liposomes can markedly inhibit murine B-16 melanoma pulmonary metastases and promote the splenocytic proliferation of the B-16-bearing mice. The antitumor and immuno-potentiating bioactivities of IL-2 liposomes are equivalent to that of free IL-2 in 5-fold dosage.