Table 1.

Different types of nanoparticles used on spinal cord injury.

Nanoparticles	Synthesis characteristics	Advantages	Results after SCI	References
Iron oxide	Superparamagnetic iron oxide NPs (IONPs) sizes vary from 5 to 300 nm.	Permit for cell recognition following cellular implantation into the SC.	Cells with internalized IONPs can be tracked in vivo using magnetic resonance imaging (MRI). Iron oxide-labeled MSCs were targeted after SCI using magnetic fields.	(44, 45)
Noble metal/nanorods	Polyethylene glicol (PEG) is mostly applied for the efficiency of NPs circulation and tissue diffusion because of their surface, facilitating the penetration of NPs into the CNS. This is allowed mainly by increasing their stability on circulation, decreased capacity to form conglomerates and their linkage with plasm and proteins further and high dissolution degree by hydrophilic character.	Chemistry modification techniques are readily done to PEG in order to add other particles onto their surface.	PEG coated on the surface of gold NPs (GNPs) has shown to enhance recovery after SC injuries. NPs covered with gold tissue engineering scaffolds have already demonstrated in vitro to promote axonal growth in neurons. In vitro neurons with gold nanorods after being exposed to radiation with a 780-nm laser displayed higher axonal and dendrite regeneration in comparison with control models in absence of radiation, as a result, they could be used after SCI with restoring effects. For the 15-nm gold NPs are, as well, employed as adjuvants for protein immunization, improving their effects, besides increasing neurite outgrowth.	(28, 46–49)
Quantum dots	Quantum dots (QD's) are crystalline semiconductors, which structure is regularly compound by a semiconducting material inside (usually cadmium or zinc) added to a stabilizing exterior. Their sizes range from 1 to 10 nanometers.	QDs mainly function as probes that display high fluorescent intensity, have wide absorption and narrow emission spectra, and are photobleaching resistant, on account of their size-induced quantum confinement. Unfavorably, experimental cultures and NS models carried out in a living organism have shown toxicity, which confines their current use for research purposes solely, mostly for cell imaging.	QD's performance was tested within a chick embryo SC model, and their mobility was tracked during development by fluorescence techniques. The implementation of ZnO QD's is mainly for neuron recount in SC murine models. Moreover, immunohistochemistry has been applied to QD's in reason of tracking astrocytes in SC.	(50–52)
Polymer NPs	Polymer NPs have variable uses in the SC and most importantly for delivery. The proportions of NPs can be broad from 50 to 1,000 nm, and also mainly present a spherical shape.	Synthetic polymers such as PLGA, (PLLA), and polycyanoacrylate are considered natural polymers that have demonstrated low toxicity levels in the CNS, allowing their role in the local delivery of therapies to the SC. Between these, the PLGA is approved by the FDA and European Medicines Agency (EMA). FA–GCNPs in various drug delivery systems, leading PLGA-based NPs to a convenient situation for clinical trials.	Biodegradable polymers such as PLGA have the capability of drug release from delivery systems and in diverse studies could be used as tissue scaffolds. PLGA offer the possibility to prevent drug depletion and improve their cohesion. In pursuance of confirming the efficacy of PLGA in drug delivery system, Lowry et al., encapsulated sonic hedgehog (Shh) into PLGA microspheres and examined whether the release of Shh by these microspheres at SCI is able to aid in the regenerative process by inducing prominently oligodendrocyte and neuron proliferation. They showed that biodegradable PLGA microspheres function as minimally invasive tools for the delivery of therapeutic agents to the injury site. In a different study, PLGA NPs approach was for local delivery of flavopiridol (cyclin-dependent kinase CDK inhibitor) to injury site, cavity formation and neural loss was decreased, additionally, it enhanced neuronal regeneration.	(29, 31, 53–56)
Dendrimer NPs	Dendrimers display a vastly ramified 3D architecture with an initiator core. Repeating units conform the inside, and various active terminal groups cover the surface. Dendrimer sizes applied in the CNS vary from 5 to 200 nm.	Dendrimers NPs are capable of delivering therapeutics for regeneration after SCI.	Following of lateral hemisection to the SC model in rats SCI, dendrimers were used for methylprednisolone delivery following SCI injection of these NPs improved BBB (standardized open-field locomotor scale for recovery) scoring to 4 weeks in contrast with controls.	(57–59)
Lipid NPs	Lipid NPs used in the CNS are usually liposomes, conformed by phospholipids or amphipathic lipids, which size varies from 20 to 100 nm.	The lipid NPs can transport lipophilic drugs due to their biocompatibility, biodegradability, and the low toxicity shown in in vivo models These are considered a novel nanocarrier for drug administration because they can transfer the BBB.	After SCI in a study, the use of liposomes decreased macrophage migration inhibitory factor, reducing secondary injury after SC on a contusion model in rats.	(32, 33, 60)
Carbon-based NPs/CNPs	CNPs applied in the SC include fullerenes and carbon nanotubes as single-wall (0.4–3 nm diameter) or multi-wall (1.4–100 nm diameter).	Fullerenes have shown neuroprotective features in vivo as a result of their chemical ability to neutralize free radicals.	CNPs have been under trial within multiple animal models of CNS injury. Multi-wall with Nogo-66 receptor siRNA, RhoA siRNA, and brain-derived neurotrophic factor DNA, has been probed after SCI in rats, were these presented elevated BBB scores at 8 weeks. Single-wall improved BBB scores of SC-injured rats 7 weeks following SCI. Fullerenes have also been applied to murine models of amyotrophic lateral sclerosis and experimental autoimmune encephalomyelitis. Regardless of its advantages, toxicity concerns remain and must be cleared to their approval for clinical use.	(39, 61–63)
SNPs	SNPs, whose proportions vary from 5 to 1,000 nm, can be assembled mesoporous (pore size 2–50 nm), providing them a wide exterior area, which enables them to load drugs extensively within the porous structure, advantage that has been applied on SC.	SNPs initial effect seems to depend on the concentration (higher concentrations are associated with cell toxicity and death).	SNPs supplied to an ex vivo guinea pig SC model, demonstrated the ability to seal neuronal membranes following SCI, however, it is necessary to prove their biocompability.	(36, 37, 56)