Carbohydrates based stimulus responsive nanocarriers for cancer-targeted chemotherapy: a review of current practices

Figures & data

Table 1. Carbohydrate based stimuli-responsive nanocarriers for cancer treatment

Stimuli	nanocarriers	Drug	Cancer	Characteristics	References
pH	drug-conjugated glycopolymer-coated gold NPs	Doxorubicin	Cervical and lung cancer	The NPs selectively released the drug in cancer cells than in healthy cells	[47]
	β-cyclodextrin decorated mesoporous materials	5-fluorouracil	Human glioma U87 MG cells	The NPs exhibited a 60% release at pH 5 and did not release the drug at neutral pH.	[49]
	β-CD-capped DOX-loaded MSN	DOX	HER2-positive breast cancer cells	The NPS exhibited HER2-mediated endocytosis and exerted the significant cytotoxicity toward HER2-positive SKBR3 cells	[50]
	Hydroxypropyl – cyclodextrin based liposomes	paclitaxel	lung adenocarcinoma (A549/T) cell line	They exhibited pH triggered PTX release with improved intracellular accumulation leading to a significant reduction in tumor growth	[51]
	Lithocholic acid and two β-cyclodextrin terminated poly(2-(dimethylamino)ethyl methacrylate) segments	DOX	Breast cancer MCF-7 cells	The carrier exhibited much quicker at pH = 5 than at pH = 7.4 and more efficiently deliver the DOX into the cancer cells due to their different drug release behaviors in the endosome acid condition.	[52]
	Core–shell tecto dendrimers (CSTDs)	DOX	HeLa cells	The nanocarrier provided the frequent release under a slightly acidic pH leads to enhanced intracellular uptake and increased anticancer activity	[53]
Temperature	β-cyclodextrin based multifunctional nanogels	DOX	human epithelial carcinoma cell line, KB cells	Nanogel shrinkage occurs under the influence of temperature switching from 25–42°C and released the encapsulated DOX in KB cells	[71]
	β-cyclodextrin anchored magnetic mesoporous silica nanoparticles	DOX	–	PNIPAM shell collapsed above the lower critical solution temperature and the release of the drug increased	[73]
	graphene oxide (GO) functionalized with carboxymethyl chitosan (CMC), and lactobionic acid (LA)	DOX	liver cancer cell line SMMC-7721	LA-containing composite selectively induces cell death in cancerous cells	[74]
	Pectin-conjugated magnetic GO nanocarrier	paclitaxel	MCF-7 cancer lines	The nanosystem revealed a significant inhibition of MCF-7 cancer cell growth	[75]
	Magnetic hydrogels composed of tragacanth gum poly(acrylic acid) and Fe3O4 nanoparticles	DOX	human epidermoid-like carcinoma (Hela) cells	Fe3O4 NPs induced hyperthermia therapy locally raises the temperature inside the Hela cells at 45 ± 3°C and promotes cell death	[78]
Magnetic	β-cyclodextrin-conjugated superparamagnetic iron oxide	Paclitaxel	HeLa, MCF-7 and CT26 cells	Superparamagnetic iron oxide nanoparticles in the nano-assembly permitted the rapid and efficient targeted drug delivery	[79]
	GA-coated MNP	Rhodamine B	9 L glioma tumors	GA-MNP accumulated 12-fold more in brain tumors than in the healthy brain	[80].
GSH/ Redox	Magnetic iron oxide nanoparticles (MNP) coated with gum arabic (GA)	Chlorambucil	MCF-7 cancer cells	The nanovesicles demonstrated increased selectivity and therapeutic effectiveness when compared to free chlorambucil	[84].
	Glycopolypeptide-based bioactive stimuli-responsive micelles	Rhodamine B	liver cancer cells (HepG2)	Dox-loaded micelles enter into the cancer show a suitable pharmacological effect on the tumor cell	[85]
	Hexadecanol-modified chitosan oligosaccharide polymer micelle coated with hyaluronic acid	Gambogic acid	triple-negative breast cancer	Complex micelle enhanced TNBC tumor cellular uptake and fast drug release due to CD44 receptor-mediated internalization and redox/pH dual-responsive drug release	[87]
	polypeptide nanogel of methoxy poly(ethylene glycol)-poly(L-phenylalanine-co-L-cystine	DOX	4T1 breast cancer treatment	Reduction-responsive polypeptide nanogel simultaneously released the drugs to the tumor cells and synergistically performed antitumor efficacy.	[88]
Enzyme	Supramolecular assembly employing biocompatible sulfato-cyclodextrin	Prodigiosin	MCF-7 and HepG2 cancer cells	drug-loaded NPs kill cancer cells more efficiently via drug release mediated by various enzymes i.e. amylase and hydrolase	[90]
	Nanometric silica mesoporous supports capped with “saccharides	Doxorubicin	HeLa cells	With the addition of galactosidase, DOX release was greatly increased, and effectively internalized by HeLa cells	[92]
	Guar gum-based matrix tablets were loaded with curcumin	Curcumin	Colon cancer	Tablets containing 40% guar gum released 91% of the active ingredient during 24 hours and effectively target the colon cancers	[93]
	Mannose-6-phosphate (M6P) based vesicle	Doxorubicin	HEK-293 cells	M6P lipid assembly underwent morphology change under the influence of enzyme which leads to effective cargo release from the system	[94]
Ultrasound	Ocarboxymethyl chitosan nanodroplets	Doxorubicin	The human prostate cancer cell line PC-3	The viability of PC-3 cells in the O-CS-DOX NDs group was significantly lower than that in the DOX group with ultrasonic irradiation	[99]
	Chitosan-alginate nanoparticles	pAcGFP1-C1 plasmid	HeLa cells and 293 T cells	The prepared nanoparticles protected the DNA from enzymatic digestion and improved the efficiency of gene transfection of HeLa cells and 293 T cells	[100]

Figure 1. The adsorption and release characteristics of 5-FU loaded on pH stimuli-responsive DDSs were investigated. Reproduced with permission from [49].

Figure 2. The development of a pH-sensitive acetylated α-CD based PTX nanoformulation is shown schematically (Ac-aCD). Reproduced with permission from [59].

Figure 3. Photo-controlled HA-NB-SC nanomicelles for CD44-mediated transport and UV light-triggered intracellular release of DOX in HeLa cells are shown schematically. Reproduced with permission from [66].

Figure 4. The formation of β-CD-hybridized nanogels (PNAC) through in situ radical polymerization and their drug loading/release characteristics are shown schematically. Reproduced with permission from [71].

Figure 5. Overall experiment depicting the use of pPTX/CD-SPION nano assembly for magnetically guided delivery of drugs in anticancer treatment. Reproduced with permission from [79].

Figure 6. Synthesis and Self-Assembly of Amphiphilic Star Co-Glycopolypeptides into Uncross-Linked (UCL) and Interface Cross-Linked (ICL) Micelles for Targeted and Controlled Drug Delivery. Reproduced with permission from ACS 2019 [85].

Figure 7. Ultrasound-triggered drug release from targeted nanoparticles. The controlled ultrasound beam is focused on the tumor tissue; nanocarriers passing through the high-intensity focused beam are disrupted or activated. Reproduced with permission from [116].

Table 1 illustrates the various Carbohydrate based stimuli-responsive nanocarriers for cancer treatment.

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