Table 1.

Representative DHA-based NDDSs with in vivo data.

DHA formulation	Cancer Type	Animal model	Dosage	Route	Safety issues	Ref.
Tf-8arm-PEG-DHA NPs	Lewis lung carcinoma	LLC tumor-bearing female C57BL/6 mice	5 mg/kg or 10 mg/kg DHA every 2 d	IV injection	Reduced hypersensitivity reactions; no severe hematotoxicity	[101]
DHA-PEG-PTX nanosystems	Colorectal cancer	HT-29 tumor-bearing Balb/c nude mice	5 mg/kg PTX and 10 mg/kg DHA every 3 d	IV injection	No significant body weight loss	[102]
DHA/MPEG-PCL NPs	Cervical cancer	HeLa tumor-bearing female athymic BALB/C nude mice	20 mg/kg DHA every 2 d	IV injection	No significant pathological changes, weight loss or inflammatory lesions	[104]
DOX and DHA coencapsulated Soluplus®-TPGS mixed micelles	Breast cancer	MCF-7 xenografted female BALB/c nude mice	15 mg/kg DHA and/or 15 mg/kg DOX every 2 d	IV injection	Reduced the cardiotoxicity; avoided hepatic damage and necrosis	[105]
OxPt/DHA core-shell particles	Colorectal cancer	CT26 or MC38 tumor-bearing BALB/c, C57Bl/6 wild-type or Rag2−/− mice	8 mg/kg OxPt, 2.86 mg/kg DHA, and/or 75 µg PD-L1 antibody every 3 d	IP injection	Reduced peripheral neuropathy	[106]
R8 modified epirubicin–DHA liposomes	Non-small-cell lung cancer	A549 tumor-bearing BALB/c nude mice	3 mg/kg epirubicin; (epirubicin/DHA= 1:5, molar ratio) every 2 d	IV injection	Neglected systemic toxicity	[116]
LDLR-targeted lipid NPs coloading sorafenib and DHA	Hepatocellular carcinoma	HepG2 tumor-bearing BALB/c nu/nu nude mice	5 mg/kg SRF and/or DHA every 3 d	IV injection	Reduced body weight loss as compared to free drugs	[118]
Alkyl glycoside-modified DHA liposomes	Hepatocellular carcinoma	H22 tumor-bearing specific-pathogen-free ICR mice	70 mg/kg DHA everyday	IP injection	No significant body weight loss	[23]
Mannosylated liposomes coloading DOX and DHA	Colon cancer	HCT8/ADR xenografted female BALB/c nude mice	1.5 mg/kg DOX and 60 mg/kg DHA every 2 d	IV injection	Avoided hepatic damage, multi-focal necrosis or apoptosis	[119]
Tf-decorated, DHA, L-buthionine-sulfoximine, and CellROX-loaded liposomes	Hepatocellular carcinoma	HepG2 tumor-bearing specific pathogen-free female BALB/c nude mice	0.9 mg/kg DHA everyday	IV injection	No noticeable sign of organ damage	[120]
Magnetic DHA nano-liposomes	Head and neck squamous cell carcinoma	Cal-27 xenografted male BALB/c mice	10 mg/kg DHA everyday	IV injection	No significant body weight loss	[22]
FeTB2@DHA-INPs	Breast cancer	MCF-7 tumor-bearing male BALB/c mice	1.64 mg/kg FeTB2 and 0.11 mg/kg DHA every 3 d	Intratumoral administration	No significant organ damage or inflammation lesion	[121]
DHA and Tf dual-dressed nano-GO	Breast cancer	EMT6 tumor-bearing female Balb/c mice	0.2 mg/kg DHA every 2 d	IV injection	No significant pathological changes or weight loss	[25]
Folate-grafted PEG-MMSNs@DHA	Hepatocellular carcinoma	HepG2 tumor-bearing BALB/c nude mice	10 mg/kg DHA every 2 d	IV injection	A large amount of nanocarriers were excreted through feces and urine 24 h after injection; no significant side effects	[127]
MnMgFe-layered double hydroxide loaded with DHA	Breast cancer	4T1 tumor-bearing female Balb/c mice	0.4 mg LDH and 0.2 mg DHA every 2 d	IV injection	No obvious side effects	[128]
DHA@ZIF-8 NPs	Hepatocellular carcinoma	H22 tumor-bearing Kunming mice	5 mg/kg DHA every 2 d	IV injection	Negligible systemic toxicity	[26]
DHA-loaded Fe-doped ZIF-8 NPs coated with HepG2 cancer cell membranes	Hepatocellular carcinoma	HepG2 tumor-bearing male BALB/c nude mice	100 µg DHA and 140 µg Fe/ZIF-8 every 3 d	IV injection	No distinct hepatic or renal toxicity; no obvious organ damage	[135]
DHA@Fe3O4@C@MIL-100(Fe) (DHA@FCM)	Cervical cancer	HeLa tumor-bearing female BALB/c nude mice	223 µg DHA and 277 µg FCM every 3 d	IV injection	No appreciable pathological changes or inflammatory lesion	[136]
MOFs-MB-DHA@PLA@PEG	Cervical cancer	U14 tumor-bearing Kunming mice	160 µg MOFs, 16 µg DHA and 0.32 µg of MB every 2 d	IV injection	No significant body weight loss	[137]
Fe-TCPP nanoscale MOF@DHA @CaCO3	Breast cancer	4T1 tumor-bearing BALB/c mice	4 mg/kg MOF (dose of DHA is calculated based on the loading content of DHA in NMOF@DHA)	IV injection	No significant body weight loss, acute toxicity, organ damage or inflammatory lesions	[138]