High drug-loading nanomedicines: progress, current status, and prospects

Figures & data

Table 1 Overview of two strategies of fabricating high drug-loading nanomedicines with porous materials as carriers

Strategy	Structure diagram	Main drug-loading mechanism	Application range	Drug-loading content	References
Inorganic porous materials as carriers	MSNPs/MCSNPs/MMSNPs MCNPs MMCNCs	Noncovalent electrostatic and/or π–π stacking and/or hydrogen bond and/or hydrophobic interaction with carry materials	Hydrophobic drugs mostly; peptides, proteins, and gene drugs sometimes	≤69.3 wt% ≤59.7 wt% ≤35 wt%	^Citation11, ^Citation27^–^Citation37, ^Citation39^–^Citation42, ^Citation48 ^Citation12, ^Citation57, ^Citation59^–^Citation64, ^Citation63, ^Citation73, ^Citation78 ^Citation80^–^Citation84, ^Citation88, ^Citation90, ^Citation95
MOFs as carriers	MOFs	Coordinate bond and/or π–π stacking and/or hydrophobic interaction	Hydrophobic drugs mostly; gas drugs sometimes	≤58.3 wt%	^Citation108^–^Citation120
Protein NPs as carriers	PNPs	Covalent bond with protein scaffold and/or π–π stacking, hydrophobic interaction with surface of PNPs and/or crystallization	Hydrophobic drugs mostly; peptides and gene drugs sometimes	≤44.9 wt%	^Citation122^–^Citation126

Abbreviations: MCNPs, mesoporous carbon nanoparticles; MCSNPs, mesoporous calcium silicate nanoparticles; MMCNCs, mesoporous magnetic colloidal nanocrystal clusters; MMSNPs, mesoporous magnesium silicate nanoparticles; MOFs, metal-organic frameworks; MSNPs, mesoporous silica nanoparticles; PNPs, protein nanoparticles; wt, weight.

Figure 1 Preparation and temperature-dependent working mechanism of the cationic, thermosensitive, copolymer-capped MSNPs.

Abbreviations: MSNPs, mesoporous silica nanoparticles; NIPAAm, N-isopropylacrylamide; BVIm, butyl vinylimidazolium.

Figure 2 Synthesis, drug loading, and surface modification of MCNPs.

Abbreviations: MCNPs, mesoporous carbon nanoparticles; DSPE, 1,2-distearoyl-sn-glycero-3-phosphoethanolamine; mPEG, methoxy polyethylene glycol; oMCNs, oxidized mesoporous carbon nanospheres; Dox, doxorubicin; PEG, polyethylene glycol.

Figure 3 Dox encapsulation in HMCNCs and pH-stimulated release of Dox from folate–HMCNC-Dox.

Abbreviations: Dox, doxorubicin; HMCNC, hollow magnetic colloidal nanocrystal; PAA, polyacrylic acid.

Figure 4 Formation of absorption/desorption-type MOF-based nanomedicine and MBioF-type nanomedicine by coordination-directed self-assembly processes.

Abbreviations: MOF, metal–organic framework; MBioF, metal–biomolecule framework.

Table 2 Overview of two strategies of fabricating high drug-loading nanomedicines with drug as part of carrier

Strategy	Structure diagram	Main drug-loading mechanism	Application range	Drug-loading content	References
Polymer-drug conjugates	Linear polymer–drug conjugate Branched polymer–drug conjugate	Covalent bond with polymer	Hydrophobic drugs mostly; codelivery with hydrophilic drug/gene drugs sometimes	≤58 wt% ≤45 wt%	^Citation131^–^Citation135 ^Citation13, ^Citation136^–^Citation143, ^Citation145^–^Citation154, ^Citation156^–^Citation158
ICP I-type nanomedicines	ICP I-type nanomedicines	Coordinate bond	Drugs with complexing ability (both hydrophobic drugs and hydrophilic drugs)	Not shown	^Citation160, ^Citation161, ^Citation164, ^Citation165

Abbreviations: ICP, infinite coordination polymer; wt, weight.

Figure 5 Amphiphilic CPT–polymer conjugates (OEG-CPT and OEG-DiCPT) and their self-assembly into nanocapsules to load other hydrophilic drug.

Note: OEG-DiCPT means two CPT molecules were conjugated to one OEG molecule.

Abbreviations: CPT, camptothecin; OEG, oligoethylene glycol.

Figure 6 Formation of mPEG-b-Dox micelles.

Abbreviations: mPEG, methoxy polyethylene glycol; Dox, doxorubicin.

Figure 7 Formation of ICP I-type nanomedicine and ICP II-type nanomedicine and their pH-responsive release.

Abbreviation: ICP, infinite coordination polymer.

Table 3 Overview of three strategies of carrier-free nanomedicines

Strategy	Structure diagram	Main drug-loading mechanism	Application range	Drug-loading content	References
Drug nanocrystals		Crystallization	Hydrophobic drugs mostly	≤93.3 wt%	^Citation21, ^Citation169^–^Citation180, ^Citation182^–^Citation200
Amphiphilic drug–drug conjugate		Covalent bond	Hydrophobic–hydrophilic drug pairs	≤ 100 wt%	^Citation201^–^Citation204
CP nanoparticles	MBioFs ICP II-type	Coordinate bond	Drugs with complexing ability (both hydrophobic drugs and hydrophilic drugs)	≤75 wt% ≤79.1 wt%	^Citation207 ^Citation209^–^Citation213

Abbreviations: CP, coordination polymer; MBioFs, metal–biomolecule frameworks; ICP, infinite coordination polymer; wt, weight.

Figure 8 Preparation and functionalization of MDNCs.

Abbreviations: MDNC, multidrug nanocrystal; PEG, polyethylene glycol; PMH, polymaleic anhydride-alt-1-octadecene.

Figure 9 Ir-Cb ADDC following natural method (A) and CPT-FUDR ADDCs following modified method (B).

Abbreviations: Ir, irinotecan; Cb, chlorambucil; ADDCs, amphiphilic drug–drug conjugates; CPT, camptothecin; FUDR, fluorodeoxyuridine; DCC, dicyclohexylcarbodiimide; DMAP, dimethylaminopyridine; RT, room temperature; DMSO, dimethyl sulfoxide.

Figure 10 Synthesis and functionalization of Tb(III)-DSCP ICPs.

Notes: Reprinted (in part) with permission from Rieter WJ, Pott KM, Taylor KM, Lin WB. Nanoscale coordination polymers for platinum-based anticancer drug delivery. Journal of the American Chemical Society. 2008;130(35):11584–11585. Copyright © 2008 American Chemical Society.²¹²

Abbreviations: DSCP, disuccinatocisplatin; ICPs, infinite coordination polymers; NCP, nano-coordination polymer; PVP, polyvinylpyrrolidone; TEOS, tetraethyl orthosilicate.

Scheme 1 Fabrication strategies of high drug-loading nanomedicines.

Abbreviations: MSNPs, mesoporous silica nanoparticles; MCNPs, mesoporous carbon nanoparticles; MMCNCs, mesoporous magnetic colloidal nanocrystal clusters; MOFs, metal–organic frameworks; LPDCs, linear polymer–drug conjugates; BPDCs, branched PDCs; ICP, infinite coordination polymer; DNCs, drug nanocrystals; ADDCs, amphiphilic drug–drug conjugates; MBioFs, metal–biomolecule frameworks.

Table 4 Overview of two strategies used for minority-specific nanomedicines

Strategy	Structure diagram	Main drug-loading mechanism	Application range	Drug-loading content	References
Noncovalent assembly		Noncovalent electrostatic and/or π–π stacking and/or hydrogen bond and/or hydrophobic interaction in drug pairs	Water-soluble drugs (both hydrophilic drugs and water-soluble hydrophobic drugs under certain conditions)	100 wt%	^Citation14
Multiple assembly		Noncovalent electrostatic and hydrophobic interaction in drug-carrier pairs	Specific drug pairs (both hydrophobic drugs, hydrophilic drugs and gene drugs)	26.4 wt%	^Citation214, ^Citation215

Abbreviation: wt, weight.

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