Solid Tumor Therapy Using a Cannon and Pawn Combination Strategy.
Solid Tumor Therapy Using a Cannon and Pawn Combination Strategy.
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使用大炮和典当组合策略的实体瘤治疗
作者：
Song W;Tang Z;Zhang D;Wen X;Lv S;Liu Z;Deng M;Chen X
基于纳米载体的抗肿瘤药物在实体瘤的治疗中具有减少副作用和改善肿瘤部位药物滞留的巨大前景。然而，治疗结果仍然有限，主要是因为药物在大多数肿瘤组织中缺乏渗透性。在此，我们提出了一种使用基于纳米载体的血管干扰剂(VDA)和细胞毒药物的组合来治疗实体肿瘤的策略。具体地说，抗肿瘤药物A-4(CA4)在远离血管的地方充当“大炮”，消灭肿瘤细胞；与此同时，阿霉素(DOX)则充当“棋子”，杀死血管附近的肿瘤细胞。这种“炮和卒”的组合策略不需要穿透每一个肿瘤细胞，有望消灭实体肿瘤中的所有肿瘤细胞。在小鼠C26结肠癌模型中，这种策略被证明有效地根除了94%以上的肿瘤细胞，并通过每周注射有效地抑制了肿瘤的生长。在大型实体肿瘤模型(C26和4T1肿瘤，体积约为250mm3)中，该策略也被证明对抑制肿瘤生长有效。这些结果显示对肿瘤生长有明显的抑制作用，为实体瘤的治疗提供了有价值的选择。
Nanocarrier-based anti-tumor drugs hold great promise for reducing side effects and improving tumor-site drug retention in the treatment of solid tumors. However, therapeutic outcomes are still limited, primarily due to a lack of drug penetration within most tumor tissues. Herein, we propose a strategy using a nanocarrier-based combination of vascular disrupting agents (VDAs) and cytotoxic drugs for solid tumor therapy. Specifically, combretastatin A-4 (CA4) serves as a “cannon” by eradicating tumor cells at a distance from blood vessels; concomitantly, doxorubicin (DOX) serves as a “pawn” by killing tumor cells in close proximity to blood vessels. This “cannon and pawn” combination strategy acts without a need to penetrate every tumor cell and is expected to eliminate all tumor cells in a solid tumor. In a murine C26 colon tumor model, this strategy proved effective in eradicating greater than 94% of tumor cells and efficiently inhibited tumor growth with a weekly injection. In large solid tumor models (C26 and 4T1 tumors with volumes of approximately 250 mm3), this strategy also proved effective for inhibiting tumor growth. These results showing remarkable inhibition of tumor growth provide a valuable therapeutic choice for solid tumor therapy.