Table 3.

Application of nanosized calcium phosphate in drug delivery.

Structural form	Materials	Size/Shape	Drug	Features/Functions	Disease/Cells	Ref.
Mix-CaP	Sodium citrate	129 ​nm Spherical	miR-133	Synthesized via a straightforward one-pot protocol	Cardiovascular disease	[56]
	Adenosine 5′-triphosphate	150–240 ​nm Spherical	Doxorubicin	Sonochemical synthesis	human gastric carcinoma cancer	[57]
	Alendronate	∼130 ​nm Spherical	pDNA ovalbumin	Mannose- and BP-dual modified	E.G7 tumor cells	[58]
	PDADMAC PAS	72 ​nm Spherical	Docetaxel	Self-assembly by using two oppositely charged templates	Human gastric carcinoma cancer	[59]
	Sodium silicate	50–70 ​nm Spherical and porous	ASODNs	Double reverse emulsion approach	Cervical carcinoma cancer	[60]
	PLGA	207 ​nm Spherical	pDNA	Water-in–oil–in water (w/o/w) double emulsion solvent evaporation method	Human embryonic kidney 293 cancer	[61]
	Methylcellulose	40–50 ​nm	–	One-pot synthesis to prepare thermo-sensitive hydrogel	Bone regeneration	[62]
Polymer-Shell	LPEI	304 ​nm Spherical	miR-34a	Coated by a long chain miRNA-34a conjugate and LPEI	Human prostate cancer	[51]
	PEG-bisphosphonates	160 ​nm Spherical	pDNA	Coated by PEG-bisphosphonates Stable over 72 ​h	Cervical carcinoma cancer	[63]
	PEG-alendronate	260 ​nm Spherical	siBcl-2	Coated by PEG- alendronate Stable over 1 month	Cervical carcinoma cancer	[35]
	PEG-PAsp(DET)	40 ​nm Spherical	siLuc	pH-responsive	Pancreatic cancer	[50,64]
	PEG-PAA	140 ​nm Spherical	siGL3	pH-responsive	Human 293 ​cells	[65,66]
	PEG–SS–siRNA	100 ​nm Spherical	siRNA	Redox-responsive	Huh-7 ​cells	[67]
	mPEG-b-PLG-g-GEM	122 ​nm Spherical	Gemcitabine	cathepsin B- responsive	Pancreatic cancer	[68]
	Chitosan-glutamine	119 ​nm Spherical	Noggin siRNA	Enhanced the cellular uptake	Stem cells	[69]
	Chitosan-dopamine	131 ​nm Spherical	pDNA and siRNA	Enhanced the cellular uptake	COS-7 ​cells	[70]
	Carboxymethyl chitosan, KALA	237 ​nm Spherical	Doxorubicin	Enhanced the cellular uptake by KALA	Hela cells	[71]
	Thiolated hyaluronic acid	168 ​nm Vermicular/Spherical	siRNA	Disulfide cross-linked HA as an anionic shell	B16F10 ​cells	[36]
	Dopamine-hyaluronic acid	63–278 ​nm Spherical	siRNA	Enhanced the cellular uptake by targeting CD44	HT-29 ​cells	[72,73]
	Alendronate- hyaluronic acid	170 ​nm Spherical	siEGFR	Enhanced the cellular uptake by targeting CD44	A549 ​cells	[34]
	PLGA	200 ​nm Spherical	pDNA	PLGA as the shell by W/O/W double emulsion method	HEK293 ​cells	[61]
	Heparin	<50 ​nm Spherical	Doxorubicin	Heparin/CaCO3/CaP mixed nanoparticles	Hela cells	[74]
	Citrus pectin, carboxymethyl-β-cyclodextrin	108 ​nm Spherical	Paris saponin VII	Enhanced the cellular uptake, NPs stable within 18 days	Orthotopic drug-resistant colon cancer	[75]
	Arg-Gly-Asp peptide sequence RGD	150/15 ​nm needle	siRNA	Enhanced the cellular uptake	A549 cancer cells	[76]
Lipid-Shell	DOTAP, Cholesterol, DSPE-PEG-AA IGEPAL–CO–520	80 ​nm Spherical	siRNA	LCP-1: prepared by the reverse microemulsion method	H-460 ​cells	[77]
	Cholesterol, DOTAP, DOPA, DSPE-PEG-AA	20 ​nm Spherical	VEGF siRNA and gemcitabine	LCP-2: Codelivery of VEGF siRNA and gemcitabine in a single nanoparticle	Orthotopic xenograft NSCLC	[78]
	DOPA, DOPC, FA-DSPE-PEG	40 ​nm Spherical	CD siRNA α-Tocopheryl succinate	Targeting combinate treatment of cancer	Melanoma	[79]
	CHOL-AA, DOTAP, DOPA, CHOL-AA-Cit	80 ​nm Spherical	siBcl-2	Charge reversible property to enhance the activity	A549 cancer cells	[80]
	PAMAM dendrimers DOPA, DOPC, DOTAP, SP94-DSPE-PEG	110.5 ​nm Spherical	PD-L1 and pDNA	Dual-targeted immunogene therapy against cancer	Hepatocellular carcinoma	[81]
	DOTAP, DOPE, DOPE-CDM-PEG	42 ​nm Spherical	miRNA-155	Microemulsion to form miRNA loaded lipid coated CaP and then coating with PEG-lipid in organic phase	Murine sarcoma cancer	[82]
	PEI-Chol, DOPE, Pluronic F68	207 ​nm Spherical	siVEGF	Film dispersion hydrated method with CaP nanoparticle solution	MCF-7 cancer cells	[83]
	DOPA, PLGA-PEG	30–80 ​nm Sphericity of cluster	miRi-221/222 and paclitaxel	Co-encapsulate miRi-221/222 and paclitaxel in different area for combination	MDA-MB-231 cancer cells	[84]
Muti-Layer	Viral antigen hemagglutinin (HA)	200–300 ​nm Spherical	CpG	Triple shell calcium phosphate-CpG-CaP-HA	Dendritic cells	[85,86]
	PEI25k	316 ​nm agglomeration	siTNF-a	Triple shell calcium phosphate-siRNA-CaP-PEI	MODE-K cells	[87]
	Octa-arginine (R8)	220–580 ​nm agglomeration	pDNA	Triple shell calcium phosphate-DNA-CaP-R8	hMSC and hOB cells	[88]
	poly-(l-lysine) (PLL)	100–250 ​nm Spherical and polyelectrolyte films	shRNA	Triple shell calcium phosphate-DNA-CaP-PLL	human osteoblasts	[89]
	Chitosan, alginate	35 ​nm Spherical	BSA or OVA	Triple shell CaP-Chi-Alg NPs as an oral vaccine delivery vehicle	Caco-2 and RAW264.7 ​cells	[90]
CaP Shell	Gold nanoparticle Polydopamine (PDA)	∼100 ​nm nanohybrids	glucose oxidase (GOx)	Gold nanoparticle core and calcium phosphate shell (Au@PDA@CaP)	–	[91]
	mesoporous silica	∼50 ​nm Spherical	doxorubicin	SiO2 core and calcium phosphate shell	Breast cancer MCF-7 ​cells	[92]
	mesoporous silica PNiPAM/AA	∼100 ​nm Spherical	doxorubicin	SiO2 core coated with PNiPAM/AA and CaP, decorated with transferrin (Tf)/RGD ligand	HepG2 and HUVEC cells	[93]
	Fe3O4, PEI	185–257 ​nm Spherical	DNA or doxorubicin	SPIONs@PEI-CPs/DNA or doxorubicin	A549/HepG2 cancer cells	[94]
	PEG-b-poly (benzoxaborole) (PEG-PBO)	140 ​nm Spherical	siRNA	pH-responsive siRNA delivery	MDA-MB-231 ​cells	[95]
	PEG-PAA, poly (Pt (IV) prodrug	85 ​nm Spherical	Pt (IV)	High drug loading efficiency and capacity	A549 cancer cells	[96]
	lipid-PEI, PAsp	∼770 ​nm	pDNA	Mineralization responsibles for higher transfection efficiency	MC3T3-E1 cells	[97]
	PLLA, DOPA, DSPE-PEG	170 ​nm Spherical	miR-21 and doxorubicin	The CaP-coated hybrid lipid-polymeric NPs	MDA-MB-231/A549 cancer cells	[98]
	NaCas	150–200 ​nm Spherical	Curcumin	Robust stability, controlled release	A549 cancer cells	[99]
	Zn(II)-dipicolylamine, hyaluronic acid	124 ​nm Spherical	siRNA and doxorubicin	Cationic derivatives to incorporate nucleic acid derivative.	OVCAR8/ADR cancer cells	[100]