Porous Carbon Nanomaterials Based Tumor Targeting Drug Delivery System: a Review

doi:10.15541/jim20200240

Abstract

Abstract:

Chemotherapy is the main method used for cancer treatment. However, most chemotherapeutic drugs show low selectivity towards tumor cells. When killing tumor cells, chemotherapeutic drugs can also damage normal tissue cells and induce a series of side effects and toxic reactions, such as gastrointestinal reactions, calvities and so on. An effective way to reduce the adverse drug reactions is to construct targeted delivery systems based on the microenvironment properties of tumor tissue. Porous carbon nanomaterials (PCN), with excellent properties such as good structural stability, pores, and easily modified surface, are promising candidate to be used for such strategy. In this paper, the construction and application of the PCN-based targeted antitumor drugs delivery system were reviewed; the structural properties, the design philosophy of PCN suitable for drug loading were summarized; the effective strategies to improve drug loading on PCN for combined drug delivery were discussed both theoretically and experimentally. The mechanism and applications of PCN for tumor microenvironment based targeted delivery system were analyzed from the perspectives of endogenous sensitive stimulations (such as acidity, redox potential and specific enzyme), exogenous sensitive stimulations (such as light and magnetic) and multiple sensitive stimulations (such as double sensitive stimulations, including acidity/redox potential, acidity/magnetic and magnetic/light, and three sensitive stimulation, including acidity/redox potential/light). The biocompatibility and biodegradability of PCN used as anti-tumor drug delivery system was discussed, and the possible solutions were analyzed. The prospects of the application of PCN to be used in tumor drugs were discussed at the end of this review. This review provides theoretical basis and examples towards design and synthesis of porous carbon (PC) materials based anti-tumor drug delivery system, which may help the research and development of targeted and controllable tumor treatment.

Key words: porous carbon nanomaterials, structural design, antitumor, targeting, drug delivery systems, review

CLC Number:

TQ174

CHENG Xiaokun, ZHANG Yue, Lü Haijun, LIU Xinying, HOU Senlin, CHEN Aibing. Porous Carbon Nanomaterials Based Tumor Targeting Drug Delivery System: a Review[J]. Journal of Inorganic Materials, 2021, 36(1): 9-24.

Figures/Tables 15

Table 1 Preparation of porous carbon nanomaterials

Preparation	Basic steps	Ref.
Hard template method	Impregnate the preformed hard template with carbon source, then remove the template after pyrolysis at a high temperature	[29-30]
Soft template method	Through surfactant assembly, the template is removed after pyrolysis at high temperature	[31-33]
Direct pyrolysis method	Direct pyrolysis of carbon precursors, such as MOF, biomass, ionic liquid or polymer	[34-37]
Chemical vapor deposition method	Introducing two or more gaseous carbon precursors into the tubular quartz reactor, carbon materials obtained through pyrolysis	[38-40]

Fig. 1 Schematic illustration of template method for synthesis of PCN[41] (a) Soft template method; (b) Hard template method

Fig. 2 Schematic illustration of direct pyrolysis methods for synthesis of porous carbon nanomaterials (PCN) (a) Preparation of MOF and porous carbon (PC)[58]; (b) Preparation of PC from plant tissue[59]; (c) Preparation of PC from PAN-co-PPy[60]; (d) Preparation of PC from PMMA-co-PS[61]

Fig. 3 (a) Schematic illustration of the preparation of DOX and FA conjugate with f-PCN to form CB-DOX/FA, and (b) the loading of DOX inside the pores and at the surface of functionalized PCN (f-PCN)[71]

Fig. 4 Schematic preparation of DOX loaded on oxide mesoporous carbon nanospheres (OMCN) and its channel capped by the interaction of π-π[75]

Fig. 5 Schematic illustration of preparing combined administration of (a) hierarchical hybrid dual-pore core-shell mesoporous carbon@silica[81] and (b) PHCNs-PEI-PEG for drug and gene co-loading[82] DOX: doxorubicin; PEI; polyethyleneimine; PEG: poly (ethylene glycol); RF: resorcinlo-formaldehyde

Table 2 Construction of tumor targeting drug delivery system based on porous carbon nanomaterials

Structure	Response modes	Drugs	＞啊.
Porous carbon sphere	pH	Mitoxantrone HCl	[87]
Porous carbon sphere	pH	Doxorubicin	[26]
Porous carbon sphere	Specific enzyme	Doxorubicin	[91]
Porous carbon derived from ZIF	Specific enzyme	Methylene blue	[35]
Porous carbon sphere	Redox potential	Doxorubicin	[93]
Hollow porous carbon sphere	Near infrared	Doxorubicin	[82]
Porous carbon sphere	Near infrared	Doxorubicin	[98]
Porous carbon sphere coated with Fe₃O₄	Magnetic	Doxorubicin	[102]
Mesoporous carbon sphere	pH-redox potential	Doxorubicin	[104] [105]
Porous carbon sphere	pH-magnetic	Doxorubicin	[106]
Ordered mesoporous carbon sphere	pH-magnetic	Doxorubicin	[107]
Ordered mesoporous carbon spheres coated with Fe₃O₄	Magnetic-near infrared	Doxorubicin	[108]
Porous carbon spheres coated with Au and Fe₃O₄	Magnetic-near infrared	Doxorubicin	[109]
Hollow porous carbon sphere	pH-redox potential-near infrared	Doxorubicin	[110]

Fig. 6 Schematic illustration of pH-responsive controlled release of ZnO-gated MCNs[87] MCN: mesoporous carbon nanoparticles

Fig. 7 Schematic illustration of enzyme-responsive of porous carbon obtained from ZIF pyrolysis [35]

Fig. 8 Schematic illustration of modified porous hollow carbon spheres and the photothermal therapy[98]

Fig. 9 Schematic illustration of MCNs coated Fe3O4 nanoparticles and DOX loaded[102] PCCMNs: porous carbon coated magnetic nanoparticles; DOX: doxorubicin; 1 Oe≈79.62 A/m

Fig. 10 Schematic preparation of MCN responsive controlled release by pH and glutathione[105] PAA: polyacrylic acid; PEI: polyc (ethyllene glycol); DOX: doxorubicin

Fig. 11 Schematic illustration of construction of pH and magnetic composite sensitive materials by flower-like porous carbon composite (FPCS)[106] DOX: doxorubicin

Fig. 12 Schematic illustration of construction drug delivery by pH and magnetic composite sensitive[108] OMCNs: ordered mesoporous carbon nanospheres; MOMCNs: magnetically OMCNs; TMOMCNs: thermo-sensitiuely MOMCNs; SMOMCNs: silane modified MOMCNs; DOX: doxorubicin

Fig. 13 Schematic preparation of stimuli-responsive MHPCNs based drug delivery system for synergistic pH, glutathione and photothermal of tumor chemotherapy[110] MHPCNs: magnetic hollow porous carbon nanoparticles

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