Silk is a sustainable and ecologically friendly biopolymer with a robust clinical track record in humans for load bearing applications, in part due to its excellent mechanical properties and biocompatibility. Our ability to take bottom-up and top-down approaches for the generation of silk (inspired) biopolymers has been critical in supporting the evolution of silk materials and formats, including silk nanoparticles for drug delivery. Silk nanoparticles are emerging as interesting contenders for

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... drug delivery and are well placed to advance the nanomedicine field. This review covers the use of Bombyx mori and recombinant silks as an anticancer nanomedicine, highlighting the emerging trends and developments as well as critically assessing the current opportunities and challenges by providing a context specific assessment of this multidisciplinary field. AIMS Bioengineering Volume 4, Issue 2, 239-258. after which it spends 72 hours spinning the up to 1500 m long and 20 m thick single silk thread that forms its cocoon. Over five millennia, humans have perfected sericulture (i.e. silk farming), so that the global silk production is now 100,000 tonnes per annum. Silk has been used in textiles for thousands of years [2] and as a suture material for many centuries [3] . Humans have long appreciated the mechanical strength, toughness and elasticity of silk fibres; these properties arise from the unique hierarchical structure of the fibre [1,4,5,6]. Since the 1990s, we have seen a tremendous development of both bottom-up and top-down approaches for the generation of silk (inspired) biopolymers [4] . Specific critical developments have included reverse engineering of silk cocoons and the advent of recombinant technologies, which have supported the exploitation of silk materials for use in a broad range of applications while reaffirming the uniqueness of in vivo-derived silk fibres [1, 7] . For example, the remarkable properties of silk have supported high-end applications, such as its use in parachute cords [8], bulletproof vests [9], composite materials for the aviation industry [10], artificial silk fibre spinning [11] , all-water-based microfabrication procedures [12] , and silk-based photonics [13], electronics and sensors [14] , as well as edible food packaging [15, 16] and in vitro tissue and disease models [17] . Regulatory authorities across the globe have approved Bombyx mori silk fibres for loadbearing applications in humans. This usage has served as a springboard for the exploration of silk for a range of medical applications, such as tissue engineering [18, 19] and drug and cell delivery [20, 21] . Overall, silk is remarkable because it can be (i) stronger than steel and tougher than Kevlar, (ii) processed in all an aqueous environment, (iii) readily formulated into many different formats (e.g. fibres, films, scaffolds, hydrogels, microparticles, nanoparticles, etc.) (Figure 1 ) [22] , and (iv) generally regarded as biocompatible and biodegradable [23] . Furthermore, silk can protect therapeutic payloads, such as low molecular weight drugs (e.g. antibiotics), macromolecules (e.g. antibodies, enzymes) [24] and cells [22] . These unique features have supported a staggering array of applications that exploit this biopolymer. Over the past 5 years, we have witnessed an increasing number of studies that have examined the potential of silk as a drug delivery intermediary, often in the context of cancer. For example, encouraging results have been obtained with in vivo focal therapy of human orthotopic breast cancer and neuroblastoma using cytotoxic chemotherapy and precision medicines using silk films [22, 25, 26] and self-assembling silk hydrogels [27, 28] . The experimental findings now warrant the development of second-generation materials. Clinical experience demonstrates that focal therapy of solid tumours is critical in improving patient outcomes in the long term; therefore, a strong demand exists for locally applied drug delivery systems that can support therapy (reviewed in [29] ). However, patient survival is poor once disseminated disease is diagnosed [30], because metastasis is responsible for 90% of the mortality of patients with solid tumours [31] . Therefore, targeting a therapeutic payload to a (metastatic) solid tumour is an appealing strategy; a concept conceived and championed by Paul Ehrlich more than 100 years ago [32] . Nanoparticles have emerged as a potential platform for drug targeting. Here, we review silk nanoparticles in the context of anticancer drug delivery and assess some of the current opportunities and challenges. Many excellent reviews covering silk for drug delivery in general [20, 21] , as well as the manufacture of silk nanoparticles in particular [33, 34] , already exist.