Table 1.

Various silk fibroin formulations for local delivery of therapeutic agents in cancer treatment.

Biomaterial Format	Released Therapeutic	Target	In Vitro/ In Vivo Model	Findings	Ref
Film	Doxorubicin	Breast cancer	MDA-MB-231/ Orthotopic adrenal tumor xenograft in mice	Sustained release over 4 weeks Doxorubicin release rate could be controlled by manipulating silk crystallinity and beta-sheet content Doxorubicin-loaded silk films significantly greater inhibited primary tumor than intravenously administered drug Silk films loaded with doxorubicin reduced metastatic spread, no local or systemic toxicity	[25]
	Doxorubicin	Neuroblastoma	KELLY, SK-N-AS, IMR-32, SH-SY5Y/ Tumor xenograft in mice	Controlled and sustained drug release up to 30 days Slower tumor growth after treatment with controlled-release silk film Effective treatment by combining surgical resection and local treatment with doxorubicin-loaded films	[148]
	Doxorubicin, Crizotinib	Neuroblastoma	KELLY/ Orthotopic tumor xenograft in mice	Sustained drug release up to 28 days Controllable release kinetics from the silk films by changing the amount and physical crosslinking of silk Intratumoral application of drug-loaded films was more effective in vivo comparing with systemic application of drugs	[167]
	Vincristine, Doxorubicin	ND	ND	Sustained drug release up to 14 days Control over drug release by altering silk film crystallinity and chemical composition	[168]
Fiber mat	Curcumin, Doxorubicin	ND	ND	Dual drug delivery (curcumin-loaded nanoparticles and doxorubicin-loaded core/shell nanofibers) and sustained release Control over the amount of drug release from nanofibers by adjusting the crystal content of nanofibers with the water-annealing process at a different temperature, release up to 40 h	[169]
	Curcumin	Colorectal carcinoma	HCT-116/ Tumor xenograft in mice	Curcumin-loaded nanofibrous matrices had enhanced anti-cancer effect as compared to free drug No toxic effect on normal NCM-460 cells Implantation of curcumin-loaded nanofibrous matrices resulted in tumor growth inhibition in vivo	[158]
Gel	Vincristine, Doxorubicin	Neuroblastoma	KELLY/ Orthotopic tumor xenograft in mice	Dual drug delivery and sustained release of drugs up to 25 days Intratumoral delivery of vincristine and doxorubicin significantly slowed tumor growth and increased drug availability as compared to intravenous administration	[23]
	Vincristine, Doxorubicin	Ewing’s sarcoma	A-673/ Tumor xenograft in mice	Combination of vincristine-loaded silk gels and doxorubicin-loaded silk foams Delivery of vincristine inside the sarcoma tumor with silk gel decreased tumor growth more effectively compared to silk foam	[170]
	Vincristine	Neuroblastoma	KELLY/ Orthotopic tumor xenograft in mice	Sustained release silk gels, Multiple injections of vincristine-loaded silk gels suppressed tumor growth Tumor growth more significantly suppressed by distributed injections compared to central injections of drug-loaded silk gel	[140]
Hydrogel	Doxorubicin	Breast cancer	MDA-MB-231, MCF-7/ Tumor xenograft in mice	Controlled doxorubicin release Doxorubicin-loaded silk hydrogels reduced primary and metastatic tumors growth Reduced toxicity compared to systemic drug administration	[26]
	Doxorubicin	Breast cancer	MDA-MB-231/ Tumor xenograft in mice	Silk hydrogels displayed thixotropic capacity allowing for easy injectability Sustained drug release over 8 weeks Dox-loaded silk hydrogels had a superior antitumor response in vitro and in vivo than free Dox	[171]
Foam	Vincristine	Neuroblastoma	KELLY/ Orthotopic tumor xenograft in mice	Sustained drug release from the foam format over 21 days	[24]
	Vincristine, Doxorubicin	Neuroblastoma	KELLY/ Orthotopic tumor xenograft in mice	Sustained drug release High drugs concentrations within the tumor resulting in slower tumor growth with less post-treatment side effects than equivalent systemic chemotherapy	[23]
Reservoir	Anastrozole	ND	ND/ Sprague-Dawley rats	Biocompatibility of silk reservoir rods Sustained drug delivery for 91 days measured in a pharmacokinetic study in vivo Biodegradation profile suitable for long-term sustained delivery of breast cancer therapeutics	[139]
	Cisplatin	Neuroblastoma	KELLY/ Orthotopic tumor xenograft in mice	Controlled release of the drug up to 30 days Intratumoral implantation of silk reservoirs decreased tumor growth significantly when compared to free cisplatin	[149]
Wafer	Etoposide	Neuroblastoma	KELLY/ Orthotopic tumor xenograft in mice	Silk coated 6% wafers released the drug up to 45 days, while uncoated wafers for 30 days Intratumoral implantation was effective at decreasing tumor growth. Etoposide-loaded silk wafers induced tumor necrosis	[138]
	Vincristine	Neuroblastoma	KELLY/ Orthotopic tumor xenograft in mice	Sustained drug release from the wafer reservoir for 7 weeks Intratumoral injection slowed tumor growth and increased drug availability as compared to intravenous administration	[24]
Microneedles	Doxorubicin, Rhodamine, ICG	Cervical cancer	HeLa/ Live mouse skin	Microneedles fabricated using a PDMS mold packed with a fibroin scaffold Controlled release up to 144 h More rapid release of doxorubicin from the microneedles with a higher proportion of sucrose Tumor cell viability decreased faster under higher sucrose content in the applied microneedles The soluble sucrose content and fibroin scaffold within microneedles accelerated the transdermal release of the photothermal agent in vivo	[137]

Dox, doxorubicin; ICG, indocyanine green; PDMS, polymethylsiloxane; ND, not determined.