Abstract
Nanomedicines are extensively employed incancer therapy. We here propose four strategic directions to improve nanomedicine translation and exploitation. (1) Patient stratification（成層庄蹋，層理） has become common practice in oncology drug development. Accordingly, probes and protocols for patient stratification are urgently needed in cancer nanomedicine, to identify individuals suitable for inclusion in clinicaltrials. (2) Rational（合理的嫩絮，理性的泻骤；有理數(shù)） drug selection is crucial for clinical and commercialsuccess. Opportunistic choices based on drug availability should be replaced byinvestments in modular (pro)drug and nanocarrier design. (3) Combination therapiesare the mainstay of clinical cancer care. Nanomedicines synergize withpharmacological and physical co-treatments, and should be increasinglyintegrated in multimodal combination therapy regimens. (4) Immunotherapy isrevolutionizing the treatment of cancer. Nanomedicines can modulate thebehaviour of myeloid(骨髓的) and lymphoid（淋巴的） cells, thereby empowering anticancer immunityand immunotherapy efficacy. Alone and especially together, these fourdirections will fuel and foster the development of successful cancernanomedicine therapies.
納米藥物廣泛用于癌癥治療。我們?cè)谶@里提出四個(gè)戰(zhàn)略方向戏羽，以改善納米醫(yī)學(xué)的轉(zhuǎn)化和開(kāi)發(fā)担神。 （1）患者分層已經(jīng)成為腫瘤藥物開(kāi)發(fā)中的普遍做法。因此始花，在癌癥納米醫(yī)學(xué)中迫切需要用于患者分層的探針和方案妄讯，以鑒定適合納入臨床試驗(yàn)的個(gè)體。（2）合理的藥物選擇對(duì)于臨床和商業(yè)成功至關(guān)重要衙荐±袒樱基于藥物可得性的機(jī)會(huì)選擇應(yīng)被模塊化（前）藥物和納米載體設(shè)計(jì)的投資所取代。（3）組合療法是臨床癌癥治療的主要手段忧吟。納米藥物與藥理和物理共同治療具有協(xié)同作用砌函，應(yīng)越來(lái)越多地整合到多模式聯(lián)合治療方案中。（4）免疫療法正在徹底改變癌癥的治療方法。納米藥物可以調(diào)節(jié)髓樣和淋巴樣細(xì)胞的行為讹俊，從而增強(qiáng)抗癌免疫力和免疫治療功效垦沉。這四個(gè)方向，尤其是一起仍劈，將推動(dòng)并促進(jìn)成功的癌癥納米醫(yī)學(xué)療法的發(fā)展厕倍。
Nanomedicine holds potential to improve anticancer therapy1. Traditionally, nanomedicines are used to modulate the biodistribution and the target site accumulation of systemically administered chemotherapeutic drugs, thereby improving the balance between their efficacy and toxicity. In preclinical settings, nanomedicines typically increase tumour growth inhibition and prolong survival as compared to non-formulated drugs, but in clinical practice, patients often only benefit from nanomedicines because of reduced or altered side effects2. Despite the recent approval of several nanomedicinal anticancer drugs, such as Onivyde (liposomal irinotecan) and Vyxeos (liposomal daunorubicin plus cytarabine), the success rate of clinical translation remains relatively low. In this context, the striking imbalance between the ever-increasing number of preclinical studies reporting the development of ever more complex nanomedicines on the one hand, and the relatively small number of nanomedicine products approved for clinical use on the other hand, has become the focus of intense debate3,4. Multiple biological, pharmaceutical and translational barriers contribute to this imbalance5. Biological barriers include tumour (and metastasis) perfusion, permeability and penetration, as well as delivery to and into target cells, endo/lysosomal escape, and appropriate intracellular processing and trafficking. Pharmaceutical barriers encompass both nanoformulation- and production-associated aspects. These range from a proper stability in the bloodstream, a beneficial biodistribution, an acceptable toxicity profile, and rational mechanisms for drug release, biodegradation and elimination, to issues related to intellectual property position, cost of goods, cost of manufacturing, upscaling and batch-to-batch reproducibility. In terms of clinical translation, the key challenge is to select the right drug and the right combination regimen, and to apply them in the right disease indication and the right patient population.
